Publications by authors named "Xavier Adhoute"

45 Publications

Expected outcomes and patients' selection before chemoembolization-"Six-and-Twelve or Pre-TACE-Predict" scores may help clinicians: Real-life French cohorts results.

World J Clin Cases 2021 Jun;9(18):4559-4572

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France.

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.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223847PMC
June 2021

Transarterial chemoembolization (TACE) plus sorafenib: a real winning combination?

Ann Transl Med 2020 Dec;8(23):1616

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.21037/atm-20-4268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791214PMC
December 2020

"Six-and-twelve" score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort.

World J Hepatol 2020 Aug;12(8):525-532

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France.

The "six-and-twelve" (6&12) score is a new hepatocellular carcinoma (HCC) prognostic index designed for recommended transarterial chemoembolization (TACE) candidates. Quick and easy to use by the sum of tumor size (cm) and number, this model identifies three groups with different survival time (the sum is ≤ 6; or > 6 but ≤ 12; or > 12); a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve. Recently, Wang ZW et al showed that the "6&12" model was the best system correlated with radiological response after the first TACE. Thus, we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC) staging, Albumin-Bilirubin grade, tumor nodularity, infiltrative nature of the tumor, alpha-fetoprotein, Child-Pugh class, and Performance Status score, Cancer of the Liver Italian Program, Model to Estimate Survival for HCC scores, up-to-seven criteria) different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled. As previously demonstrated, we show that the "6&12" score can classify survival within this French cohort, with a prognostic value comparable to that of other systems, except HKLC staging. More importantly, the "6&12" score simplicity and ability in patients' stratification outperform other systems for a routine clinical practice.
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http://dx.doi.org/10.4254/wjh.v12.i8.525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475776PMC
August 2020

ALBI-based BCLC nomogram: A new or an additional prognostic tool?

Liver Int 2020 07 23;40(7):1785-1786. Epub 2020 Mar 23.

Department of Gastroenterology and Hepatology, Hôpital Universitaire de l'Archet, Nice, France.

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http://dx.doi.org/10.1111/liv.14431DOI Listing
July 2020

Sorafenib: Experience and Better Manage-ment of Side Effects Improve Overall Survival in Hepatocellular Carcinoma Patients: A Real-Life Retrospective Analysis.

Liver Cancer 2019 Nov 27;8(6):457-467. Epub 2019 Mar 27.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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; < 0.01) and mOS (8 vs. 12 months; < 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; < 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.
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http://dx.doi.org/10.1159/000497161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883434PMC
November 2019

Prognostication of HCC under sorafenib: Is it always possible?

Liver Int 2020 05 26;40(5):1241-1243. Epub 2019 Nov 26.

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph Marseille, Marseille, France.

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http://dx.doi.org/10.1111/liv.14294DOI Listing
May 2020

The "six-and-twelve score" for TACE treatment: Does it really help us?

J Hepatol 2019 11 9;71(5):1051-1052. Epub 2019 Sep 9.

Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de Nancy, France.

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http://dx.doi.org/10.1016/j.jhep.2019.06.014DOI Listing
November 2019

NIACE score refines the overall survival of hepatocellular carcinoma by Barcelona clinic liver cancer staging.

J Gastroenterol Hepatol 2019 Dec 18;34(12):2179-2186. Epub 2019 Jun 18.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background And Aim: The NIACE score provides prognostic values for hepatocellular carcinoma (HCC) in European studies. We aim to evaluate the prognostic value of the NIACE score in Asian patients.

Methods: Patients with HCC were retrospectively enrolled from a tertiary medical center in Taiwan during 2009-2014, and their clinical information were collected. The NIACE score was calculated according to the Nodular numbers, tumor Infiltration, Alpha-fetoprotein level, Child-Pugh score, and Eastern Cooperative Oncology Group score. The prognostic values of NIACE score for overall survival according to individual treatment and the Barcelona clinic liver cancer (BCLC) staging were analyzed.

Results: A total of 468 patients were included with a median follow-up of 30 months. A greater NIACE score correlated with lower median survival and higher BCLC staging. Regardless of treatment modalities, NIACE scores (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival between groups (log-rank P < 0.001). Specifically, NIACE score (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival in patients receiving transarterial chemoembolization (log-rank P < 0.001). NIACE score 1, 2.5, and 4 further distinguished overall survival in BCLC A, B, and C patients, respectively (all log-rank P < 0.01). After adjustment of the confounders and the BCLC staging, NIACE score of 2.5-3 and 4-7 (vs 0) had a significantly increased risk of mortality with a hazard ratio of 4.04 (95% confidence interval: 2.14-7.64, P < 0.001) and 7.45 (95% confidence interval: 3.22-17.23, P < 0.001), respectively.

Conclusions: The NIACE score helps refine differential prognosis among BCLC A, B, and C subgroups of Asian patients with HCC, especially in those receiving transarterial chemoembolization.
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http://dx.doi.org/10.1111/jgh.14705DOI Listing
December 2019

Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort.

Eur J Gastroenterol Hepatol 2019 Nov;31(11):1414-1423

Department of Gastroenterology and Hepatology.

Background: Conventional 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 Methods: A 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.

Results: Median 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.

Conclusion: HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.
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http://dx.doi.org/10.1097/MEG.0000000000001420DOI Listing
November 2019

[Hepatitis B virus infection: control or cure?]

Rev Prat 2018 Mar;68(3):276-282

Service d'hépatogastroentérologie, hôpital Saint-Joseph, 26, bd de Louvain, 13008 Marseille, France.

Hepatitis b virus infection: control or cure? Hepatitis B virus infection remains a global public health issue with changing epidemiology due to several factors including vaccination policies and migration. Approximately 254 million individuals are chronic HBsAg carrier worldwide including around 300 000 individuals in France. Host immune response plays a key role in hepatitis B pathogenesis and clinical manifestations. Hepatitis B screening should be performed in all individual with risk factors and in patients with elevated ALT. Hepatitis B vaccination should be implemented at birth or during early childhood and in individuals with risk factors. The needs for curative treatment depend mainly on the stage of the disease. Current HBV treatment are based on long term use of nucleos(t)ide analogue and rarely on the use of finite duration of pegylated interferon. The endpoints of therapy are long-term suppression of HBV replication, biochemical response and optimally durable loss of HBsAg and anti-HBs seroconversion. Current and future research aim to develop combination with antiviral therapy targeting multiple steps in the HBV lifecycle that rapidly suppress viral replication and viral antigen production and immune modulatory therapy to restore immune response to HBV in order to achieve the goal of HBV cure.
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March 2018

Sofosbuvir, velpatasvir and voxilaprevir: a new triple combination for hepatitis C virus treatment. One pill fits all? Is it the end of the road?

Therap Adv Gastroenterol 2018 2;11:1756284818812358. Epub 2018 Dec 2.

Hepato-Gastroenterology Department, Hospital Saint Joseph, Marseilles, France.

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.
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http://dx.doi.org/10.1177/1756284818812358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295690PMC
December 2018

[Hepatocellular carcinoma: Increase in incidence or future plague?]

Bull Cancer 2018 May 19;105(5):502-507. Epub 2018 Mar 19.

Institut de cancérologie de l'Ouest, département d'oncologie médicale, site de Nantes, boulevard J.-Monod, 44805 Saint-Herblain cedex, France.

Hepatocellular carcinoma is the third most frequent cause of cancer death worldwide, particularly in Asia and Africa. Most cases complicate an underlying liver cirrhosis due to hepatitis B or C chronic virus infection or alcoholic abuse. But, following the current epidemics of obesity and type 2 diabetes, it appears that these diseases, associated in metabolic syndrome, are responsible for non alcoholic fatty liver disease at risk of HCC frequently before the stage of cirrhosis. Recent hypotheses consider that in the near future, cancer deaths due to HCC will overpass in USA those due to breast or colorectal cancers. Governments should develop policies to prevent obesity, type 2 diabetes and the metabolic syndrome as well as fight against alcoholism and hepatitis B and C virus infections.
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http://dx.doi.org/10.1016/j.bulcan.2018.02.003DOI Listing
May 2018

Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case-control study.

Eur J Gastroenterol Hepatol 2018 Apr;30(4):368-375

Departments of Hepato-Gastroenterology.

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.
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http://dx.doi.org/10.1097/MEG.0000000000001082DOI Listing
April 2018

Impact of direct-acting antiviral agents on the risk for hepatocellular carcinoma.

Transl Gastroenterol Hepatol 2017 18;2:110. Epub 2017 Dec 18.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.21037/tgh.2017.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762991PMC
December 2017

Intermediate stage treatment: Is TACE enough?

Liver Int 2018 01 23;38(1):187. Epub 2017 Oct 23.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.1111/liv.13598DOI Listing
January 2018

Response to 'the flexible therapeutic approach to the BCLC B stage': Time for scoring systems?

J Hepatol 2017 Sep 15. Epub 2017 Sep 15.

Department of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette, Marseille, France.

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http://dx.doi.org/10.1016/j.jhep.2017.07.038DOI Listing
September 2017

An in-depth review of chemical angiogenesis inhibitors for treating hepatocellular carcinoma.

Expert Opin Pharmacother 2017 Oct 14;18(14):1467-1476. Epub 2017 Sep 14.

c Department of Medical Oncology , Center Eugène Marquis , Rennes , France.

Introduction: Hepatocellular carcinoma (HCC) is a frequent and severe complication of cirrhosis. Most HCC patients initially present with or progress to advanced stage disease and require systemic treatment. As hypervascularization is a major characteristic of HCC, antiangiogenic drugs have been tested. Areas covered: In this review, we summarize data on the use of drugs targeting the angiogenesis. Despite many trials, in 2017 only 3 drugs, all antiangiogenic, have demonstrated efficacy in first (sorafenib, lenvatinib) or second line (regorafenib) treatment of advanced HCC. The heterogeneous mechanisms of action and the major reasons for failure of most trials are discussed. An English-language, abstract-based literature review was performed by a PubMed-based strategy. Expert opinion: Currently all trials based on purely antiangiogenic compounds (bevacizumab, linifanib, brivanib and ramucirumab) or drugs with strong antiangiogenic properties (sunitinib) have failed (increased toxicity, minor efficacy and/or flaws in trial design); sorafenib, lenvatinib and regorafenib are multityrosine kinase inhibitors and their efficacy can be partly related to another mechanism of action. We need to better refine future trials design (randomized phase 2, good stratification factors and marker-enriched patient selection) in order to progress toward customized treatment, perhaps in association with immunotherapy.
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http://dx.doi.org/10.1080/14656566.2017.1378346DOI Listing
October 2017

Prediction of benefit after transarterial chemoembolization (TACE): Subclassifications or scoring systems?

Liver Int 2018 01 29;38(1):184. Epub 2017 Jul 29.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.1111/liv.13516DOI Listing
January 2018

To TACE or not to TACE? Lessons from a negative trial.

Lancet Gastroenterol Hepatol 2017 08 23;2(8):541-543. Epub 2017 Jun 23.

Department of Hepatogastroenterology, Hopital Saint Joseph, Marseille, France.

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http://dx.doi.org/10.1016/S2468-1253(17)30181-4DOI Listing
August 2017

Usefulness of the MESH score in a European hepatocellular carcinoma cohort.

World J Hepatol 2017 May;9(15):711-714

Xavier Adhoute, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, 13008 Paris, France.

The Barcelona Clinic Liver Cancer classification is the most widely - used hepatocellular carcinoma (HCC) staging system because it is simple, precise and linked to a treatment algorithm based on randomized studies. But each group includes a broad spectrum of tumors, with limited therapeutic options, particularly for intermediate and advanced stages. Consequently, different additional scoring systems have been proposed to refine the prognosis and/or to improve the management. But until now, there is no consensus. Liu et al proposes a new scoring system, based on a large HCC cohort, with patients at different stages, treated using diverse modalities. This score includes six parameters used in current practice. It is simple to calculate, reliable, with an ability to predict survival superior to other systems, which also works with our European HCC cohort. The MESH score may be especially useful to differentiate subgroups with different prognosis for each treatment modality.
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http://dx.doi.org/10.4254/wjh.v9.i15.711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440775PMC
May 2017

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort.

World J Gastroenterol 2017 Apr;23(14):2545-2555

Xavier Adhoute, Hervé Perrier, Paul Castellani, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, 13008 Marseille, France.

Aim: To 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.

Methods: Data 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.

Results: The 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 ( < 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.

Conclusion: In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.
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http://dx.doi.org/10.3748/wjg.v23.i14.2545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394518PMC
April 2017

NIACE score for hepatocellular carcinoma patients treated by surgery or transarterial chemoembolization.

Eur J Gastroenterol Hepatol 2017 Jun;29(6):706-715

aDepartment of Hepato-Gastroenterology bDepartment of Hepatobiliary Surgery cDepartment of Radiology, Hôpital Saint-Joseph dAlphaBio Laboratory eDepartment of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette fDepartment of Hepatobiliary Surgery, Centre Hospitalo-Universitaire Timone, Marseille gDepartment of Hepato-Gastroenterology, Centre Hospitalo-Universitaire de Nancy hINSERM U954, Université de Lorraine, CHU de Nancy, Vandoeuvre les Nancy, France.

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.
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http://dx.doi.org/10.1097/MEG.0000000000000852DOI Listing
June 2017

How to assess the efficacy or failure of targeted therapy: Deciding when to stop sorafenib in hepatocellular carcinoma.

World J Hepatol 2016 Dec;8(35):1541-1546

Jean-Luc Raoul, Marine Gilabert, Department of Medical Oncology, Paoli-Calmettes Institute, 13273 Marseille, France.

Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma (HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate (from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria (European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques (computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor (hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alpha-fetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data (in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival (Child-Pugh class, Barcelona Clinic Liver Cancer, alpha-fetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.
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http://dx.doi.org/10.4254/wjh.v8.i35.1541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165267PMC
December 2016

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments.

World J Hepatol 2016 Jun;8(17):703-15

Xavier Adhoute, Paul Castellani, Hervé Perrier, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, 13008 Marseille, France.

Therapeutic management of hepatocellular carcinoma (HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer (BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.
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http://dx.doi.org/10.4254/wjh.v8.i17.703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911504PMC
June 2016

Nomogram of the Barcelona Clinic Liver Cancer System: external validation in European patients.

Liver Int 2016 11 20;36(11):1716-1717. Epub 2016 Jun 20.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.1111/liv.13171DOI Listing
November 2016

HCC classification and HCC scoring system: a win-win combination for prognosis and treatment recommendations.

Liver Int 2016 12 29;36(12):1876-1877. Epub 2016 Apr 29.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.1111/liv.13140DOI Listing
December 2016

Hepatocellular carcinoma scoring and staging systems. Do we need new tools?

J Hepatol 2016 06 19;64(6):1449-50. Epub 2016 Feb 19.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

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http://dx.doi.org/10.1016/j.jhep.2016.01.038DOI Listing
June 2016

Staging of hepatocellular carcinoma: BCLC system, what else!

Liver Int 2016 09 30;36(9):1395-6. Epub 2016 Jan 30.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, Marseille, France.

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http://dx.doi.org/10.1111/liv.13066DOI Listing
September 2016

Prognosis of advanced hepatocellular carcinoma: a new stratification of Barcelona Clinic Liver Cancer stage C: results from a French multicenter study.

Eur J Gastroenterol Hepatol 2016 Apr;28(4):433-40

Departments of aHepato-Gastroenterology bHepatobiliary Surgery cRadiology, Hôpital Saint-Joseph dAlphaBio Laboratory eDepartment of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette, Marseille fDepartment of Hepato-Gastroenterology, Centre Hospitalo-Universitaire, Saint-André Bordeaux, Bordeaux gDepartment of Hepato-Gastroenterology and Digestive Oncology, Centre Eugène Marquis, Rennes hDepartment of Hepato-Gastroenterology iINSERM U954, Université de Lorraine, CHU de Nancy, Vandoeuvre les Nancy, France.

Background: Advanced hepatocellular carcinoma (HCC) includes a wide spectrum of tumors and patients' prognosis after treatment is highly variable. Moreover, therapeutic options based on the Barcelona Clinic Liver Cancer (BCLC) staging system algorithm are restricted to one systemic therapy.

Aim Of The Study: To refine the stratification among BCLC C HCC patients by establishing a new simple prognostic score.

Patients And Methods: A regression model based on a BCLC stage C population and validated with an external cohort of BCLC C HCC patients defined the score. It was therefore validated among three external cohorts of BCLC C HCC patients treated with sorafenib.

Results: Five variables had independent prognostic values: the number of nodules, the infiltrating nature of the HCC, α-fetoprotein serum level, Child-Pugh score, and Eastern Cooperative Oncology Group Performance Status grade. They were integrated into a new score named NIACE ranging from 0 to 7, well correlated with survival. With the use of one threshold value, this score enables defining of two populations with different survivals among BCLC C patients and specifically among those treated with sorafenib.

Conclusion: The NIACE score defines different prognostic subgroups after palliative treatment of HCC. It could be an additional tool for BCLC C HCC before inclusion in clinical trials or for the management of patients. These results must be validated in a prospective study.
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http://dx.doi.org/10.1097/MEG.0000000000000558DOI Listing
April 2016

Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection.

Expert Rev Gastroenterol Hepatol 2015 23;9(12):1483-94. Epub 2015 Nov 23.

c Alpha bio Laboratory , Hôpital Européen , Marseilles , France.

Sofsobuvir is the first-in-class NS5B nucleotide inhibitor to be launched as a treatment for the hepatitis C virus (HCV). Its viral potency, pan genotypic activity and high barrier to resistance make it the ideal candidate to become a backbone for several IFN-free regimens. Ledipasvir is a NS5A inhibitor with multi genotypic activity but modest barrier to resistance. The once-daily fixed-dose combination of sofosbuvir plus ledipasvir is the first-in-market single-tablet regimen for the treatment of hepatitis C infection. Recent data demonstrated that this FDC alone, or in combination with ribavirin, is able to achieve HCV cure of at least 90% or more among genotype 1,4, 5 and 6 patients. This combination appears to be suboptimal in genotype 3 patients and other direct acting antiviral combinations with sofosbuvir will help to fulfill this gap in the near future. The safety profile of the fixed dose combination is good. Resistance is not an issue with sofosbuvir but may be a significant issue with regards to ledipasvir for those rare individuals who harbor baseline HCV NS5A resistance-associated variants that conferred a high resistance level. The rational for using FDCs and the available clinical data are reviewed.
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http://dx.doi.org/10.1586/17474124.2015.1111757DOI Listing
September 2016
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