Liver cancer international最新文献

{"title":"Recalibrating survival prediction among patients receiving trans-arterial chemoembolization for hepatocellular carcinoma","authors":"Alessandro Cucchetti,&nbsp;Edoardo G. Giannini,&nbsp;Cristina Mosconi,&nbsp;Maria Corina Plaz Torres,&nbsp;Giulia Pieri,&nbsp;Fabio Farinati,&nbsp;Gian Ludovico Rapaccini,&nbsp;Maria Di Marco,&nbsp;Eugenio Caturelli,&nbsp;Rodolfo Sacco,&nbsp;Giuseppe Cabibbo,&nbsp;Claudia Campani,&nbsp;Andrea Mega,&nbsp;Maria Guarino,&nbsp;Antonio Gasbarrini,&nbsp;Gianluca Svegliati-Baroni,&nbsp;Francesco Giuseppe Foschi,&nbsp;Gabriele Missale,&nbsp;Alberto Masotto,&nbsp;Gerardo Nardone,&nbsp;Giovanni Raimondo,&nbsp;Gianpaolo Vidili,&nbsp;Maurizia Rossana Brunetto,&nbsp;Vito Sansone,&nbsp;Marco Zoli,&nbsp;Francesco Azzaroli,&nbsp;Franco Trevisani,&nbsp;the ITA.LI.CA Study Group","doi":"10.1002/lci2.33","DOIUrl":"10.1002/lci2.33","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (<i>R</i>²: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (<i>R</i>²: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The <i>c</i>-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"45-53"},"PeriodicalIF":0.0,"publicationDate":"2021-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45475488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary metabolites are promising non-invasive biomarkers of hepatocellular carcinoma and chronic liver disease","authors":"Courtney E. Hershberger,&nbsp;Alejandro I. Rodarte,&nbsp;Shirin Siddiqi,&nbsp;Amika Moro,&nbsp;Lou-Anne Acevedo-Moreno,&nbsp;J. Mark Brown,&nbsp;Daniela S. Allende,&nbsp;Federico Aucejo,&nbsp;Daniel M. Rotroff","doi":"10.1002/lci2.25","DOIUrl":"10.1002/lci2.25","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Improved tools are needed for detecting HCC so that treatment can begin as early as possible. Current diagnostic approaches and existing biomarkers, such as alpha-fetoprotein (AFP) lack sensitivity, resulting in too many false negative diagnoses. Machine learning may be able to identify combinations of biomarkers that provide more robust predictions and improve sensitivity for detecting HCC. We sought to evaluate whether metabolites in patient saliva could distinguish those with HCC, cirrhosis, and those with no documented liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We tested 125 salivary metabolites from 110 individuals (43 healthy, 37 HCC, 30 cirrhosis) and identified four metabolites that displayed significantly different abundance between groups (FDR <i>P</i> &lt; .2). We also developed four tree-based, machine-learning models, optimized to include different numbers of metabolites, that were trained using cross-validation on 99 patients and validated on a withheld test set of 11 patients. A model using 12 metabolites –octadecanol, acetophenone, lauric acid, 1-monopalmitin, dodecanol, salicylaldehyde, glycyl-proline, 1-monostearin, creatinine, glutamine, serine and 4-hydroxybutyric acid – had a cross-validated sensitivity of 84.8%, specificity of 92.4% and correctly classified 90% of the HCC patients in the test cohort. This model outperformed previously reported sensitivities and specificities for AFP (20-100 ng/mL) (61%, 86%) and AFP plus ultrasound (62%, 88%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Impact</h3>\u0000 \u0000 <p>Metabolites detectable in saliva may represent products of disease pathology or a breakdown in liver function. Notably, combinations of salivary metabolites derived from machine learning may serve as promising non-invasive biomarkers for the detection of HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"33-44"},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39433907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of hypoxic and metabolic gene profiling in hepatocellular carcinoma","authors":"Fabiola Milosa,&nbsp;Rosina Maria Critelli,&nbsp;Simone Lasagni,&nbsp;Alessandra Pivetti,&nbsp;Lorenza Di Marco,&nbsp;Dante Romagnoli,&nbsp;Lucia Carulli,&nbsp;Francesco Dituri,&nbsp;Serena Mancarella,&nbsp;Gianluigi Giannelli,&nbsp;Maria-Luz Martinez-Chantar,&nbsp;Luca Fabris,&nbsp;Erica Villa","doi":"10.1002/lci2.23","DOIUrl":"10.1002/lci2.23","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is characterized by high clinical and biological heterogeneity, depending on the extremely variable combinations of pathways, linked with immune mechanisms, neo-angiogenesis, ECM remodeling, metabolism and/or hypoxia. We recently identified a 5-genes neo-angiogenic transcriptomic signature (TS), able to discriminate between “aggressive” HCCs (TS-positive) from “bland” HCCs (TS negative), the former having extremely poor survival. The aim of this study was to compare gene expression of our HCC cohort with gene expression of well-characterized, published signatures, which have been related with several different functions potentially relevant in carcinogenesis (ie immune control, hypoxia, metabolism, vascular invasion). We also aimed to ascertain the prognostic power for survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The gene expression profile of a cohort of 78 HCC patients prospectively identified were analysed according to a series of published gene expression signatures related with hypoxia, metabolism and immunity and related with the ability of the signature to predict survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Only few genes described in the various immune-signatures analyzed were differentially expressed and were related with reduced survival in our prospective cohort, especially in TS-positive HCCs. Genes composing hypoxic, metabolic and vascular invasion signatures were instead much more deregulated both in aggressive or bland HCCs. For most of them, the level of expression related with reduced survival. This suggests their possible value as biomarker of tumor aggressiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Altogether, our data demonstrate that in HCC, and especially in aggressive TS-positive HCC, signaling pathways related with hypoxic and metabolic/glycolytic signatures are more relevant in determining a poorer outcome of HCC than immune-related pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 1","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"2021-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46390923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Back to the basics: How the preclinical rationale shapes the immunotherapy landscape for hepatocellular carcinoma","authors":"Antonio D’Alessio,&nbsp;Lorenza Rimassa","doi":"10.1002/lci2.24","DOIUrl":"10.1002/lci2.24","url":null,"abstract":"<p>Few types of cancers have witnessed such a dramatic change of the treatment paradigm in the last year as hepatocellular carcinoma (HCC). 2020 has been a milestone year, establishing atezolizumab plus bevacizumab as the new standard of care for first-line treatment of unresectable HCC, based on the results of the phase III IMbrave150 trial.<span>^{1, 2}</span> The success of the combination of an anti-programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) and an antiangiogenic agent is the result of a strong preclinical rationale, which has been widely studied in HCC, paving the way for its widespread clinical application. The positive results of the IMbrave150 study are just the tip of the iceberg, with several immunotherapy combinations currently under investigation in phase I-III studies. Immune checkpoint inhibitors (ICIs) used as monotherapy have led to disappointing results in HCC, both in first line, with nivolumab failing to demonstrate any survival advantage over sorafenib in the CheckMate 459 trial,<span>³</span> and in second line, with pembrolizumab not confirming the promising results of the previous phase II trial in the KEYNOTE-240 trial.<span>⁴</span> For this reason, combining ICIs with other drug classes could overcome innate tumour resistance and eventually increase the number of patients benefitting from immunotherapy. The novel treatment strategies under the spotlight include PD-1/PD-L1 mAbs plus antivascular endothelial growth factor (VEGF) mAb, PD-1/PD-L1 mAbs plus multikinase inhibitors (MKIs) and ICI combinations (PD-1/PD-L1 mAbs plus cytotoxic T lymphocyte antigen [CTLA]-4 mAbs). In preclinical studies, these combinations have shown to enhance the efficacy of the single agents, thus suggesting a potential synergistic effect.</p><p>The use of anti-VEGF agents rests on the principle that HCC is a richly vascularized cancer, and several proangiogenic factors play a central role in tumour growth and distant spread. In addition, preclinical research unravelled a whole world of immunomodulatory effects of the VEGF pathway, thus suggesting the possible use of bevacizumab in combination with immunotherapy. Indeed, VEGF receptors and the downstream effectors induce an immunosuppressive microenvironment by acting on innate and adaptive immune response. VEGF pathway can enhance the action of immature dendritic cells, myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages, while at the same time increasing the percentage and the action of regulatory T cells (T-regs) in the tumour microenvironment.<span>⁵</span> In preclinical models, the use of bevacizumab has shown to revert these VEGF-induced immunosuppressive mechanisms, and, when bevacizumab is combined with an ICI, antitumor immune response induced by PD-1 blockade seems to be enhanced, even in ICI-resistant HCC models, thanks to an immunostimulatory T cell reprogramming.<span>⁶</span> Based on a sim","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 1","pages":"5-6"},"PeriodicalIF":0.0,"publicationDate":"2021-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49490296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell mediated responses against alpha-foetoprotein in hepatocellular carcinoma: Relationship with hepatitis C virus infection, tumour phenotype and patients’ survival","authors":"David J. Pinato,&nbsp;Petros Fessas,&nbsp;Antonello Gibbin,&nbsp;Giuseppa Occhino,&nbsp;Elisa Boccato,&nbsp;Carlo Smirne,&nbsp;Rosalba Minisini,&nbsp;Mario Pirisi","doi":"10.1002/lci2.22","DOIUrl":"10.1002/lci2.22","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alpha-foetoprotein (AFP) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). However, T-cell response (TR) to AFP is suppressed in HCC due to immune evasion. It is unknown whether HCV infection may pre-condition TR against AFP, or whether TR may influence the clinical course of HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively enrolled 18 HCV+ treatment-naïve patients with cirrhosis (CC), 18 HCV+ HCC cases and 17 HCV- HCC cases. TR was quantified by ELISPOT using assays specific to interleukin (IL) 2, IL10 and granulocyte-monocyte colony stimulating factor (GM-CSF) on ex-vivo peripheral blood mononuclear cells (PBMC) stimulated in vitro with AFP peptides. Cytokine ratios were compared between groups and with clinicopathological features of HCC, including overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportion of AFP-specific responses was not different across the studied groups for any of the assayed cytokines. AFP-specific IL-2 responses were increased in larger (<i>P</i> = .02), multifocal tumours (<i>P</i> = .01) and correlated with advanced disease (<i>P</i> = .01). TRs did not correlate with other clinicopathological factors and did not predict for OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tumour stage but not HCV infection is related to the emergence of anti-AFP TRs. These data enable formulation of a rationale for the further development of anti-AFP immunotherapy in HCC, facilitating optimal patient selection for future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 1","pages":"7-14"},"PeriodicalIF":0.0,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47444442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of epigenetic alterations in aflatoxin-induced hepatocellular carcinoma","authors":"Sathish Kumar Mungamuri,&nbsp;Vijay Aditya Mavuduru","doi":"10.1002/lci2.20","DOIUrl":"10.1002/lci2.20","url":null,"abstract":"<p>Aflatoxins are produced by <i>Aspergillus flavus and Aspergillus parasiticus</i> and are toxic carcinogens. These ‘fungal molds’ grow on corn, groundnuts, cereals and other grains. Of all the aflatoxins, Aflatoxin-B1 (AFB1) is considered the most toxic. Long-term exposure of AFB1 forms DNA adducts causing many genetic mutations and epigenetic alterations, ultimately leading to hepatocellular carcinoma (HCC). The liver is the major site of Aflatoxin detoxification; wherein cytochrome P-450 (CYP450) enzymes process the AFB1 into its epoxide AFB1-Exo-8,9-Epoxy (ABFO) and other less toxic metabolites. ABFO, in turn, reacts with DNA, RNA and protein molecules forming AFB adducts. The AFB1-DNA adducts in turn will induce various mutations, mainly mediated by G→T transversions. Aflatoxins are also known to cause HCC cell proliferation, growth, and invasion as well as angiogenesis by various epigenetic mechanisms including DNA methylation, histone post-translational modifications and non-coding RNA deregulation, etc. In this review, we will be emphasizing on epigenetic mechanisms by which aflatoxins induce hepatocarcinogenesis. In the last section, we will also discuss various methodologies to control aflatoxin contamination and detoxification of aflatoxin adducts using natural substances that are potentially anti-aflatoxins.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"1 2","pages":"41-50"},"PeriodicalIF":0.0,"publicationDate":"2020-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43580404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regorafenib therapy for hepatocellular carcinoma in a HIV-1-infected patient: A case report","authors":"Mark Peter Lythgoe,&nbsp;Maximilian Julve,&nbsp;David J. Pinato,&nbsp;Rohini Sharma","doi":"10.1002/lci2.15","DOIUrl":"10.1002/lci2.15","url":null,"abstract":"<p>The availability of safe, highly active anti-retroviral therapy (HAART) has dramatically ameliorated the morbidity related to human immunodeficiency virus (HIV) infection, significantly improving life expectancy.<span>¹</span> A parallel reduction in AIDs-defining (acquired immunodeficiency syndrome) malignancies, such as Kaposi's sarcoma, primary central nervous system lymphoma and cervical cancer has also been observed.<span>²</span> Despite this reduction, rates of non-AIDs defining cancers including Hodgkin's lymphoma, anal cancer and hepatocellular carcinoma (HCC) have increased driven, at least in part, by improved overall survival.<span>²</span></p><p>The treatment armamentarium for advanced HCC has welcomed several new additions, with the development of multi-target tyrosine kinase inhibitors (TKIs) such as sorafenib and more recently lenvatinib, cabozantinib, regorafenib and the monoclonal antibody, ramucirumab.<span>^3-7</span> The pivotal phase III RESORCE trial demonstrated regorafenib efficacy as a second-line treatment for BCLC stage B or C patients previously treated with sorafenib with preserved liver function (Child-Pugh A), improving overall survival by 3 months compared to placebo.<span>^{6, 7}</span></p><p>Regulatory trials for these drugs, such as the RESORCE trial have excluded challenging patient populations, including those with concomitant HIV infection. This has led to uncertainly in terms of both safety and efficacy in these patient groups. Sorafenib has been licensed in the European Union since 2007. Following approval, evidence in the form of case reports/case series have demonstrated both the safety and utility of sorafenib in HIV-1 seropositive patients with advanced HCC.<span>^{8, 9}</span> The concomitant use of HAART and sorafenib also appears to be both safe and effective.<span>¹⁰</span> However, for newer TKIs, such as regorafenib, there is currently no published evidence to guide safe administration.</p><p>This case report describes the first reported use of regorafenib in a patient with HIV-1 infection and advanced HCC.</p><p>A 68-year-old Nepalese gentleman with a history of HIV-1 infection and cirrhosis was diagnosed in July 2018 with multifocal HCC (largest lesion 6 cm) not amenable to curative treatment. The cirrhosis was attributed to heavy alcohol intake (~80 units/wk for &gt;5 years) and was diagnosed following an episode of acute hepatic decompensation 4 years prior, involving variceal bleeding and encephalopathy. This resolved after conservative management and had not re-occurred following complete alcohol abstinence.</p><p>HIV-1 was diagnosed in 2011 following an episode of atypical pneumonia (presumed <i>Pneumocystis</i>). Tests for other viral infections, such as hepatitis B and C were negative. He was commenced on HAART at the time of diagnosis with Truvada<b>^®</b> (Emtricitabine/Tenofovir) and Efavirenz. He had c","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"1 2","pages":"51-54"},"PeriodicalIF":0.0,"publicationDate":"2020-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49068825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole exome sequencing identifies clinically relevant mutational signatures in resected hepatocellular carcinoma","authors":"Jason Y. Chan,&nbsp;Abner H. Lim,&nbsp;Arnoud Boot,&nbsp;Elizabeth Lee,&nbsp;Cedric C.-Y. Ng,&nbsp;Jing Y. Lee,&nbsp;Vikneswari Rajasegaran,&nbsp;Wei Liu,&nbsp;Shane Goh,&nbsp;Jing H. Hong,&nbsp;Xiaoying Xu,&nbsp;Lavina D. Bharwani,&nbsp;Chung Y. Chan,&nbsp;Alexander Y. F. Chung,&nbsp;Peng C. Cheow,&nbsp;Chee-Kiat Tan,&nbsp;Choon K. Ho,&nbsp;Kui H. Liau,&nbsp;Winston W. L. Woon,&nbsp;Jee K. Low,&nbsp;Akhil Chopra,&nbsp;Gilberto Lopes,&nbsp;Steven G. Rozen,&nbsp;Bin T. Teh,&nbsp;Alex Y.-C. Chang","doi":"10.1002/lci2.14","DOIUrl":"10.1002/lci2.14","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Most patients develop recurrent disease despite curative surgery for hepatocellular carcinoma (HCC). No standard adjuvant therapy is available and molecular predictors of outcome are poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a multicentre pilot study on patients with localized HCC following surgical resection. Patients received up to 6 months of oral gefitinib as adjuvant therapy. Clinical end points included recurrence-free survival (RFS) and overall survival (OS), and exploratory analyses were conducted from whole exome sequencing data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 65 patients were screened for the study, of which 40 were eligible. The median age was 63 years (range, 44-80). Most patients (80%) were positive for hepatitis B or C. With a median follow-up of 4.5 years, the median RFS was 24 months. Median OS was not reached. High Child-Pugh score and advanced T-stage (3-4) were independent predictors for both OS and RFS. Mutational signatures for exposure to aristolochic acid (AA), as characterized by a majority of T:A &gt; A:T mutations, were observed in 18 cases (55%). HCC without AA mutagenesis was associated with early recurrences or death within 2 years of surgery (<i>P</i> = .037). HCC with high T &gt; A mutations was associated with better OS (HR 0.29, 95% CI 0.09-0.90, <i>P</i> = .033). Conversely, HCC with high C &gt; T mutations was associated with worse OS (HR 4.55, 95% CI 1.20-17.31, <i>P</i> = .026).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mutational signatures may carry prognostic significance in HCC following curative resection. Patient outcomes with gefitinib as adjuvant therapy after resection for HCC were modest, highlighting the need for urgent research in this area of unmet clinical need. ClinicalTrials.gov number, NCT00282100.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"1 1","pages":"25-35"},"PeriodicalIF":0.0,"publicationDate":"2020-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47638460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of HCC recurrence after DAA treatment for HCV in a multicentre Italian cohort study","authors":"Maria Guarino,&nbsp;Giovan Giuseppe Di Costanzo,&nbsp;Dario Bruzzese,&nbsp;Anna Sessa,&nbsp;Marco Guarracino,&nbsp;Luca Rinaldi,&nbsp;Andrea Aglitti,&nbsp;Angelo Salomone Megna,&nbsp;Federica Morando,&nbsp;Nicola Coppola,&nbsp;Nicola Caporaso,&nbsp;Filomena Morisco","doi":"10.1002/lci2.13","DOIUrl":"10.1002/lci2.13","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and aim</h3>\u0000 \u0000 <p>The present real-life multicentre, prospective study aims to investigate the effects of direct-acting antivirals (DAAs) in HCV patients with a previous successfully treated hepatocellular carcinoma (HCC), in terms of neoplastic recurrence and sustained virological response (SVR) rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From March 2015 to March 2017, all consecutive HCV patients with a previous successfully treated HCC who underwent DAA therapy were enrolled. Neoplastic recurrence was used as the primary outcome, whereas the secondary outcomes were patient characteristics predicting HCC recurrence. Cumulative probabilities of recurrence were extracted from time-to-event curves based on the Kaplan-Meier method. Hazard ratios with 95% confidence intervals were estimated using univariate and multivariate Cox regressions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 101 patients were enrolled: 83% of them were in Child-Pugh class A, 88% had a history of HCC BCLC stage 0/A and 91.1% achieved SVR. The median time from the last successful HCC treatment to DAA start was 10.1 months [IQR: 5.6-16.7]. Thirty-one HCC recurrences were observed from DAA start (median follow-up: 31.7 months). The incidence rate of recurrence was 20.5/100 person-years. The 6-, 12- and 24-months HCC recurrence rates from the last HCC treatment were 1%, 8.9% and 25.6% respectively. DAA treatment failure, higher level of total bilirubin, higher BMI and higher level of AFP were significantly associated with higher risk of HCC recurrence in both univariate and Cox multivariate analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data suggest that the achievement of SVR and the absence of well-known HCC risk factors reduce  recurrence in patients who have taken DAAs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"1 1","pages":"12-24"},"PeriodicalIF":0.0,"publicationDate":"2020-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43358321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation and refinement of PROSASH model using the neutrophil-to-lymphocyte ratio in patients with HCC receiving sorafenib","authors":"Andrea Casadei-Gardini,&nbsp;Giuseppe Cabibbo,&nbsp;Vincenzo Dadduzio,&nbsp;Giulia Orsi,&nbsp;Ranka Vukotic,&nbsp;Mario Domenico Rizzato,&nbsp;Margherita Rossi,&nbsp;Valeria Guarneri,&nbsp;Sara Lonardi,&nbsp;Dario D'Agostino,&nbsp;Ciro Celsa,&nbsp;Giulia Rovesti,&nbsp;Margherita Rimini,&nbsp;Pietro Andreone,&nbsp;Vittorina Zagonel,&nbsp;Mario Scartozzi,&nbsp;Philip Johnson,&nbsp;Stefano Cascinu,&nbsp;Alessandro Cucchetti","doi":"10.1002/lci2.12","DOIUrl":"10.1002/lci2.12","url":null,"abstract":"<p>The recently developed PROSASH model is proving to be a useful tool in risk-group discrimination in hepatocellular carcinoma (HCC) patients treated with sorafenib. Several studies highlighted that the neutrophil-to-lymphocyte ratio (NLR) is one of the most important predictors of survival in HCC patients treated with sorafenib. The aims of the present study were to validate the PROSASH model and determine whether the incorporation of inflammatory markers can improve risk stratification. This study included 438 patients. According to the four categories of the PROSASH model, median overall survival (OS) was 20.0, 14.9, 8.5 and 3.0 months respectively (<i>P</i> &lt; .001). The Harrell's c for this categorized model was 0.621. NLR (cut-off 3) stratified OS in each of the PROSASH categories. After reclassification, median OS was 21.0, 15.1, 8.2 and 4.1 months (<i>P</i> &lt; .001). The Harrell's c increased from 0.621 to 0.673 (<i>P</i> = .001). Integrating NLR into the PROSASH model allowed a more accurate classification of the patients in the risk groups.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"1 1","pages":"6-11"},"PeriodicalIF":0.0,"publicationDate":"2020-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46398095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}