HCV genotype 1a and 1b: Similarities and differences in clinical features, therapeutic outcome and predictors of response

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy

Background: There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs). Aim: To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking. Methods: All subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014. Results: The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, …

Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C real life experience

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/13…

Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy

Background: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors. Methods: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-monthperiod. Results: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P…

Survival and recurrences after curative treatments of HCV-related early hepatocellular carcinoma. A meta-analysis of single arm studies

Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma

Background: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. Aim: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Methods: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Results: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6 …

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…

AISF position paper on liver disease and pregnancy.

Abstract The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disea…

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter def…

Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER)…

The association between education level and chronic liver disease of any etiology

Abstract Background The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. Aim To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. Methods Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in t…

Retrospective, observational, multicentre study on the Italian population affected by chronic hepatitis C who failed to clear HCV-RNA after the combination therapy (PEG-IFN and ribavirin): Nadir study

Entecavir effectiveness in naïve and NUC experienced patients: Interim analysis of the ENTAS cohort study of patients with chronic hepatitis B

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…

HepaDisk – A new quality of life questionnaire for HCV patients

Abstract Background Since most patients with hepatitis C virus (HCV) infection now receive treatment irrespective of liver disease severity, special attention to patient quality of life (QoL), including psycho-social aspects, is required. No QoL questionnaire is specific for patients with HCV. Aims To develop and validate a short Italian questionnaire (HepaDisk) assessing the QoL of patients affected by HCV with intuitive graphic results that is understandable by patients and physicians. Methods A questionnaire, drafted by a steering committee, underwent a Delphi survey. A multicenter, observational study was conducted to validate the developed HepaDisk versus other tools (CLDQ-I, SF-36, WP…

A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma

Background & Aims: Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals (DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV-relat…

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely t…

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

Abstract Background. Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. Aim. To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. Results. The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to …

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% a…

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…

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.

Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000–1200 mg/daily depending on body weight) was given for 24–60 (mean 39.5) weeks. Results: Biochemical …

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.

© 2019 Elsevier Ltd. All rights reserved.

Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy

AbstractNatural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mai…

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…

Consensus recommendations for managing asymptomatic persistent non-virus non-alcohol related elevation of aminotransferase levels

Abstract A persistent increase in non-virus non-alcohol related aminostransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary …

Changes in hepatocellular carcinoma aggressiveness characteristics with an increase in tumor diameter

Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were mal…

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology

Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. Abstract BACKGROUND: Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. AIM: To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. PATIENTS: Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. RESULTS: The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child…

Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network

Background: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin lev…

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…

Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Background and aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered…

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors

Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (…

Identification of Naïve Hcv-1 Patients with Chronic Hepatitis who may Benefit from Dual Therapy with Peg-Interferon and Ribavirin.

Background & Aims The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Methods In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. Results Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637…

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…

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 …

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both gro…

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…

Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance

Background & Aims In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. Results In the study cohort of 539 pa…

Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Background & Aims 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. Methods 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. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient …

An a priori prediction model of response to peginterferon plus ribavirin dual therapy in naïve patients with genotype 1 chronic hepatitis C.

none 29 no Background: Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon. +. ribavirin therapy. Methods: In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response. The model was then validated in 423 patients (validation cohort). Results: In the derivation cohort, 257 achieved rapid virological response and 8…

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid gr…

Monofocal hepatocellular carcinoma: How much does size matter?

Background & Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P…

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Abstract Aim This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results In more deprived regions, HCC was more frequently diagnosed during surveillan…

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Abstract Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveil…

Characteristics and Changes over Time of Alcohol-Related Chronic Liver Diseases in Italy

Introduction. To evaluate the characteristics of alcohol-related chronic liver disease (CLD) in Italy and their potential changes over time. Patients and Methods. Subjects with CLD were enrolled in two national surveys performed in 2001 and in 2014 in Italy. The two surveys prospectively recruited patients aged ≥ 18 years referring to more than 80 Italian liver units scattered all over the country using similar clinical approach, analytical methods, and threshold of risky alcohol intake definition (≥ 3 units/day in men and ≥ 2 units/day in women). Results. Out of 12,256 enrolled subjects, 2,717 (22.2%) reported a risky alcohol intake. Of them, anti-HCV positive was observed in 48.3% of subj…

The Italian ENTAS cohort study: Entecavir effectiveness in naïve and treatment experienced patients with chronic hepatitis B

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regres…

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome.

Aim: To evaluate similarities and differences in HCV-1 subtypes 1a and 1b in the presenting clinical features and the response to peg-interferon and ribavirin (Peg/RIBA).Patients and methods: A total of 1,233 naïve patients with HCV genotype-1 infection, 159 (13 %) with subtype 1a and 1,074 (87 %) with subtype 1b were treated with Peg-IFN/RIBA at 12 Italian centers. Covariates included in the logistic model were age, gender, BMI, serum alanine aminotransferase, serum gamma-glutamiltranspeptidase (γGT), platelets counts, liver fibrosis, the occurrence of type 2 diabetes, baseline viremia, and IL28B genotype.Results: At multivariate analysis, baseline characteristics differentiating patients …

Long-term use of human albumin for the treatment of ascites in patients with hepatic cirrhosis: The interim analysis of the ANSWER study

s / Digestive and Liver Disease 47S (2015) e1–e18 e7 (months; 95% CI): CPT 0 62 (52.9–71.1), A 44 (41.6–46.4), B 22 (19.7–24.3), C 9 (6.6–11.3), p<0.0001. Comparisons between survivals of CTP 0 vs A, B and C were also statistically different (p<0.0001 in all associations). The prognosis of patients in the intermediateBCLCstagealsodifferedaccording to the liver function (0 vs A vs B, p<0.0001). Conclusions: The newly proposed CTP class 0 identifies a different subgroup of patientswith a better prognosis, alsowhen applied in a European cohort, where HCV aetiology is predominant. This new approach impacts not only on outcome prediction but also, potentially, on treatment allocation, better str…

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 (…

Geographical pattern of chronic liver diseases in Italy: Results from two pooled national surveys

Background: The information on the geographical characteristics of chronic liver diseases (CLD) in Italy is out-dated. Aim: To provide up-dated information on the geographical pattern of patients with CLD born in Italy. Methods: Patients with CLD were enrolled in two national surveys performed in 2001 and 2014, which prospectively recruited subjects aged ≥18 years referring to Italian liver units located throughout the country that apply a similar clinical approach and analytical methods. Results: The total number of patients enrolled was 11,676. Alcohol-related CLD was more frequently observed in northern/central areas (25.0% vs. 20.7%, p &lt; .001), while HBV-related (15.4% vs. 13.3%, p =…

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…

Epidemiological and clinical scenario of chronic liver diseases in Italy: Data from a multicenter nationwide survey

The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years. Background The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years. Methods We enrolled 2,557 CLD consecutive patients in 16 Italian liver units in 2014. Results HBV etiology accounted for 513 (20.2%) cases, alone in 439 and associated with HCV and/or alcohol abuse in 74. Of these 513, 11.9% were anti-HDV-positive and 7.2% HBeAg-positive. HCV alone was responsible for 50.3% of CLD and with alcohol abuse for 5.9%. HCV RNA was detec…

Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and w…

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis

Background The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. Objective Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. Design We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysi…

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study

Background and Aim The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). Material and Methods 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. Results The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6 to 33.2%. Regarding the age class 0–33 (fully covered by …

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), …

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…