Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor
The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using t…
Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon
none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infec…
Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma
Background & Aims Assessment of long-term outcome is required in hepatitis C virus (HCV)-infected patients with cirrhosis, who have been successfully treated for Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC). However, problems arise due to the lack of models accounting for early changes during follow-up. The aim of this study was to estimate the impact of early events (HCC recurrence or hepatic decompensation within 12Â months of complete radiological response) on 5-year overall survival (OS) in a large cohort of patients with HCV and cirrhosis, successfully treated HCC. Methods A total of 328 consecutive Caucasian patients with HCV-related cirrhosis and BC…
The evolutionary scenario of hepatocellular carcinoma in Italy: an update
Background and aims Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of etiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Methods Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centers from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). Results The main results were: 1) progressive patient aging; 2) progressive expansion of non-viral cases and, namely, of “metabolic” hepatocellular carcinoma…
Fibronectin Type III Domain–Containing Protein 5 rs3480 A>G Polymorphism, Irisin, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease
Context Contrasting data have been reported on the role of irisin, a novel myokine encoded by the fibronectin type III domain-containing protein 5 (FNDC5) gene, in nonalcoholic fatty liver disease (NAFLD) pathogenesis. We tested in patients with suspected nonalcoholic steatohepatitis (NASH) the association of FNDC5 variants, hepatic expression, and circulating irisin with liver damage (F2 to F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods We considered 593 consecutive patients who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and wit…
Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma
OBJECTIVES:The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group.METHODS:We assessed the prognosis of 269 untreated HCC patients observed in the period 1987-2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compa…
Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma
Background Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. Methods and Findings Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metas…
The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study
Background: The Italian Liver Cancer (ITA.LI.CA) prognostic system for patients with hepatocellular carcinoma (HCC) has recently been proposed and validated. We sought to explore the relationship among the ITA.LI.CA prognostic variables (ie tumour stage, functional score based on performance status and Child-Pugh score, and alpha-fetoprotein), treatment selection and survival outcome in HCC patients. Patients and Methods: We analysed 4,867 consecutive HCC patients undergoing six main treatment strategies (liver transplantation, LT; liver resection, LR; ablation, ABL; intra-arterial therapy, IAT; Sorafenib, SOR; and best supportive care, BSC) and enrolled during 2002-2015 in a multicenter It…
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial
Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly…
Pathophysiology of non alcoholic fatty liver disease
The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.
Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference.
Abstract Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent …
Years of life that could be saved from prevention of hepatocellular carcinoma
Summary Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18–61 y…
Rare ATG7 genetic variants predispose patients to severe fatty liver disease
Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-rela…
A "systems medicine" approach to the study of non-alcoholic fatty liver disease
a b s t r a c t The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diag- nosis criteria, and new endpoints of clinical trials).…
AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions
Abstract This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”. The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (…
Hepatectomy Versus Sorafenib in Advanced Non-Metastatic Hepatocellular Carcinoma: A Real-Life Multicentric Weighted Comparison
Objective: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. Background data: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. Methods: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. Results: Between 2008 and 2019, 478 patients…
A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study
Simple Summary Accurate prognostic systems capable of predicting the survival of patients with advanced hepatocellular carcinoma undergoing Sorafenib therapy are still lacking. The search for the ideal predictive tool for survival and drug response is justified by the recent availability of several other drugs effective for these patients, licensed as first- and second-line treatment, other than reducing adverse events and costs. In this study, we aimed to identify simple demographic and clinical parameters able to predict survival and Sorafenib response in a large multicenter cohort. In this study, we showed that patient’s general status, liver function and damage laboratory parameters and…