Risk of Hepatocellular Carcinoma in Patient With Liver Cirrhosis

Study of Hepatocellular Carcinoma Risk in Patient With Liver Cirrhosis

Purpose of the study is to determine transcriptomics, metabolomics and proteomics features of liver cirrhotic tissue in patients with hepatocellular carcinoma (HCC) and to find a correlation with the risk of developing HCC and survival.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Hepatocellular

Detailed Description

Patients will be enrolled after hepatic ultrasonography control and they will be submitted to hepatic vein pressure gradient and liver biopsy.

The study have four research lines:

Task # 1: transcriptomic characterization of liver tissue. During hepatic vein pressure gradient , liver tissue will be extracted with transjugular catheter equipped with a biopsy device. Tissue will be used to extract microRNA to define molecular signature.

Task # 2: Proteomic characterization of liver tissue. Protein expression changes will be analyze with MALDI-TOF

Task # 3: Metabolomic features on serum of patient with cirrhosis. Metabolomics is defined as the quantitative measurement of the dynamic multiparametric response of living systems to pathophysiological stimulus or genetic modification. Principal objective of this activity will be identify metabolites deregulated with metabolomic approach and clarify any new pathways involved in the evolution of cirrhosis to hepatocellular carcinoma.

The metabolomic analysis will be performed on sera collected in patients with cirrhosis at baseline.

Task # 4: Transcriptomic characteristics of newly diagnosed HCC. New diagnosis of hepatocellular carcinoma will undergo an eco-assisted liver biopsy. A tissue sample will be dedicated to the extraction of 'RNA. Patients will then undergo elective treatment according to international guidelines. The course of the disease and the results of therapeutic interventions will be recorded and correlated with the molecular data. Molecular signature will be obtain.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

Study Locations

• Italy
  • MO
    • Modena, MO, Italy, 41124
      • Recruiting
      • Azienda Ospedaliera Universitaria Policlinico Di Modena
      • Contact: ERICA VILLA, MD; Phone Number: 0594225308; Email: erica.villa@unimore.it
      • Contact: Email: erica.villa@unimore.it
      • Principal Investigator: ERICA VILLA, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with liver cirrhosis will be selected. After obtaining informed consent they will be submitted to hepatic biopsy,blood sample, HVPG with combined right heart catheterization and every 6 months to ultrasound.

Patients will be followed for 24 months thereafter or until the diagnosis of HCC, whichever comes first. In case of onset of HCC, will be performed a eco-guided biopsy.

Description

Inclusion Criteria:

• Obtaining written informed consent
• Liver cirrhosis
• Aged between 18 and 75 years
• Absence of exclusion criteria

Exclusion Criteria:

• HCC
• HIV
• Pregnancy
• Portal vein thrombosis
• Liver Transplant
• Patients' refusal to participate in clinical research

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptomics characterization of liver tissue: the purpose is molecular evaluation of possible predisposing factors to development of hepatocellular carcinoma in patients with cirrhosis.	RNA sample will be collected from patients and used to obtained transcriptomic profile through microarray and microRNA. Patients will be submitted to hepatic vein pressure gradient and combined right heart catheterization. During this standard procedure liver tissue will be taken and treated for extraction of RNA. In order to obtain microarray RNA extracted will be analyzed with single color hybridization of human RNA on Agilent Whole Human Genome Oligo whereas, the extraction of microRNA will be made starting from RNA extracted with mirVana miRNA Isolation kit.	December 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteomic characterization of liver tissue: the objective is to understand if there is a relationship between emergence of HCC and alterations of protein expression in cirrhotic liver.	Modifications of protein expression will be examined by two-dimensional electrophoresis and MALDI-TOF.	DECEMBER 2017
Metabolomic features of patient with cirrhosis: principal aim of this task is to identify particular metabolites and potential new pathway involved in the evolution of cirrhosis to hepatocellular carcinoma	Analysis will be conducted on sera collected during the screening. These samples will be examined using liquid chromatography and mass spectrometry in order to obtain the identification of main components and their mass than, the informations will be analyzed by MarkerLynxTM software	DECEMBER 2017
Transcriptomics characteristics of newly diagnosed hepatocellular carcinoma: the purpose is to verify if we can predict the survival of patients considering the molecular features of HCC at first diagnosis.	Patients with new diagnosis of hepatocellular carcinoma will be subjected to liver biopsy. A part of biopsy will be used to extract RNA and we will try to identify molecular signature through qRT / PCR (polymerase chain reaction) and using a set of 12 up- regulated and 10 down - regulated genes previously identified.	DECEMBER 2017

Collaborators and Investigators

• Sponsor: University of Modena and Reggio Emilia
• Investigators: Principal Investigator: ERICA VILLA, Università di Modena e Reggio Emilia

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 12, 2017
• First Posted (Actual): March 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Fibrosis; Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis
• Other Study ID Numbers: UNIRER 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No