Which are the major pathogenetic mechanisms in Viral hepatitis C?
Which are the long term clinical outcomes after definitive eradication of the hepatitis C virus by antiviral therapy?
How metabolic factors and diet contribute to the pathogenesis of esophageal cancer?

We are interested in defining pathogenetic mechanisms and clinical outcomes in hepatitis C, with specific focus on direct antiviral agents. This is approached by prospective studies in a large cohort of HCV patients which are currently followed up in the Veneto Region.
We are also investigating pathogenetic and metabolic mechanisms in the development of esophageal cancers, using a combination of animal models and human materials derived from patients at different pre-neoplastic and neoplastic stages.

Background
Research
Group Members
Key Publications

HEPATOLOGY AND GASTROENTEROLOGY

The research interest of the group, which is coordinated by Prof Alfredo Alberti, Full Professor of Gastroenterology at the University of Padova, is currently focused on two main aspects :
a) Pathogenesis and control of hepatitis C and of its clinical consequences
b) Pathogenesis, prevention, early diagnosis and innovative treatment strategies in esophageal adenocarcinoma
Ongoing research activities and future plans
Hepatitis C
The research group is currently assessing pathogenetic mechanisms and clinical outcomes of hepatitis C during and after treatment with the new oral direct antivirals (DAAs). These drugs have been become recently available and have revolutionized therapy of hepatitis C by allowing definitive eradication of the virus in the vast majority of infected patients, including those with the most advanced form of disease. However, the long term clinical benefits of this therapy remains to be defined in relation to prevention of disease complications , with all the prognostic and also pharmaco-economic implications.
Furthermore, little is known on the molecular changes occurring in the HCV genome and proteins during antiviral therapy with DAAs and on the consequences in relation to development of drug resistance.
We have therefore initiated since early 2015 at VIMM, in closed collaboration with the University of Padova, the Veneto Regional Health Authorities and the Clinical Centers of the Veneto Territory, a prospective project aimed : a) to define long term clinical outcome after DAA therapy of hepatitis C , b) to characterize virus mutants which might emerge during therapy, being responsible for treatment failure and resistance to retreatment.
The project is conducted by using a web-based platform which is recording all DAAs treatments in a vast geographic area in the North-East of Italy (The NAVIGATORE Platform). More than 9000 patients have been entered in the analysis. The project is providing novel information on the role of virus and host genetics signatures in determining the virological and clinical outcomes, including progression and regression of liver fibrosis and of portal hypertension.
We have also collected a large cohort of patients with HCV related B-cell lymphoma, allowing analysis of pathogenetic pathways and of clinical outcomes after HCV eradication also in this specific setting.
Wide genomic studies are now planned to assess genetic signatures that could be predictive of favorable or unfavorable clinical outcomes, including development of aggressive forms of hepatocellular carcinoma that we have recently described to rise in the liver of cirrhotic patients at the time of suppression of HCV replication by DAAs. Changes in the immunological and molecular liver microenvironment during and after termination of HCV replication and inflammation are also analyzed in these patients
Gastrointestinal tumors
Currently, the main focus here of our research is on pathogenesis and prevention of esophageal adenocarcinoma (EAC). The research project is coordinated by Stefano Realdon , Chief Gastroenterologist at the Istituto Oncologico Veneto in Padova and includes :
a) Evaluation of the main risk factors which might be responsible for the increasing incidence of EAC in Western Countries : in this field we are conducting an interventional study assessing the impact of lifestyle habits and of moderate caloric and protein restriction in patients with Barrett’s Esophagus, in relation to development of dysplasia or cancer. Progression of disease is correlated with a full set of metabolic and inflammatory markers measured in serum and tissue specimens and with changes in the esophageal microbiota composition driven by diet
b) Evaluation of the role of insulin resistance related factors in BE onset and evolution to cancer. In this project insulin signaling and deregulation are measured in human tissue specimens and in a hyperinsulinemic , non-obese murine model of surgically-induced EAC.
c) Identification and validation of innovative strategies to improve early diagnosis and effectiveness of therapeutic interventions for EAC. In this field we are using a combination of Confocal Endo-microscopy and of fluorescent Nanoparticles coated with a polysaccharide shell and grafted with peptides specific for esophageal cancer cells. The project, that is supported by EuroNanoMed, involves a multidisciplinary International Team from Poland, France and Italy. The nanoparticles are currently tested in our animal model of EAC to identify tumor cells in the contest of BE, and also as carriers for anticancer targeted therapy. The following steps will involve development of probes for human studies.

Stefano Realdon

MD, PhD, PI for projects of Esophageal Adenocarcinoma

Elisa Dassie

Post-doctoral Fellow

Diletta Arcidiacono

Post-doctoral Fellow

Marysol Gonzo

Post-doctoral Fellow

Daniele Nucci

Post-doctoral Fellow

Sara Piovesan

MD PhD

  1. Dassie E, Arcidiacono D, Wasiak I, Damiano N, Dall’Olmo L, Giacometti C, Facchin S, Cassaro M, Guido E, De Lazzari F, Marin O, Ciach T, Fery-Forgues S, Alberti A, Battaglia G, Realdon S. Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma. Int J Nanomedicine. 2015 Oct 30;10:6811-23.
  2. Dall’Olmo L, Fassan M, Dassie E, Scarpa M, Realdon S, Cavallin F, Cagol M, Battaglia G, Pizzi M, Guzzardo V, Franceschinis E, Pasut G, Rugge M, Zaninotto G, Realdon N, Castoro C. Role of proton pump inhibitor on esophageal carcinogenesis and pancreatic acinar cell metaplasia development: an experimental in vivo study. PLoS One. 2014 Nov 21;9-11:
  3. Kondili LA, Romano F, Rolli FR, Ruggeri M, Rosato S, Brunetto MR, Zuin M, Puoti M, Alberti A, Modelling cost-effectiveness and health gains of a “universal” vs. “prioritized” HCV treatment policy in a real-life cohort. Hepatology. 2017 Dec 66, 1814-1825
  4. Alberti A, Piovesan S. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: Fact or fiction? Liver Int. 2017 Jun;37(6):802-808.
  5. Petta S, Marzioni M, Russo P, Aghemo A, Alberti A,; 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. Lancet Gastroenterol Hepatol. 2017 Jun;2(6):427-434.
  6. Cammà C, Petta S, Cabibbo G, Ruggeri M, Enea M, Bruno R, Capursi V, Gasbarrini, A, Alberti A, Craxì A; WEF Study Group. Cost-effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C. J. Hepatol. 2013 Oct;59(4):658-66
  7. Franceschini L, Realdon S, Marcolongo M, Mirandola S, Bortoletto G, Alberti A. Reciprocal interference between insulin and interferon-alpha signaling in hepatic cells: a vicious circle of clinical significance? Hepatology. 2011 Aug;54(2):484-94
  8. Castéra L, Sebastiani G, Le Bail B, de Lédinghen V, Couzigou P, Alberti A. Prospective comparison of two algorithms combining non-invasive methods for staging liver fibrosis in chronic hepatitis C. J Hepatol. 2010 Feb;52(2):191-8.
  9. Marcolongo M, Young B, Dal Pero F, Fattovich G, Peraro L, Guido M, Sebastiani G, Palù G, Alberti A. A seven-gene signature (cirrhosis risk score) predicts liver fibrosis progression in patients with initially mild chronic hepatitis C. Hepatology. 2009 Oct;50(4):1038-44.
  10. Sebastiani G, Halfon P, Castera L, Pol S, Thomas DL, Mangia A, Di Marco V, Pirisi M, Voiculescu M, Guido M, Bourliere M, Noventa F, Alberti A. SAFE biopsy: a validated method for large-scale staging of liver fibrosis in chronic hepatitis C. Hepatology. 2009 Jun;49(6):1821-7

ALFREDO ALBERTI

  • Full Professor of Gastroenterology, Department of Molecular Medicine, University of Padova, Italy (current)
  • MD: University of Padova (1972)
  • Post-graduate degree in Hematology – University of Padova, Italy (1976)
  • Post-graduate degree in Gastroenterology – University of Padova, Italy (1984)
  • Visiting Professor – King’s College – London (1976-1979)
  • Group leader: Institute of Internal Medicine – University of Padova, Italy (since 1990)
  • Venetian Institute of Molecular Medicine, Padova, Italy (since 2001)
  • Member:
    • NIH Panel on hepatitis C (1997 and 2002)
    • NIH Consensus Panel on Hepatitis B (2000)
    • WHO Viral Hepatitis task Force (2001-2006)

Selected Awards

  • 2000 – Romania Medical Association Award
  • 2002 – Japanese Society of Gastroenterology Award
  • 2003 – Jordanian Gastroenterology Award
  • 2017 – Career Award for Hepatology – AISF