Evaluation of Risk of hEpatocellular Carcinoma

NCT06523179 | Recruiting

• 1 other identifier: PERSPECTIVE
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the second cause of cancer-related mortality worldwide. Nonalcoholic fatty liver disease (NAFLD), that is hepatic accumulation of fat in excess of 5% not explained by at risk alcohol intake, is projected to become the leading cause of HCC in Western countries within 2025.NAFLD is most frequently caused by insulin resistance due to unhealthy lifestyle. Due to the epidemics of obesity and type 2 diabetes, NAFLD now affects one in three individuals worldwide. NAFLD-HCC frequently develops without overt cirrhosis suggesting that steatosis directly promotes hepatic carcinogenesis.

Conditions

NASH; HCC; Genetic Predisposition

Outcome Measures

Primary Outcomes (2)

• The quantify the impact of genetic risk factors for NAFLD-HCC and their interaction

  The different inclusion criteria are able to identify the number of individuals at risk for NAFLD-HCC among patients with NAFLD following up, Understand the impact of individual genetic variants on HCC risk and rates of patients hosting gene mutations in evolving fat accumulation in liver (global cohorts and according to enrolment criteria)

  up to 84 months

• The quantify the impact of genetic risk factors for NAFLD-HCC and their interaction

  The impact of genetic risk factors for NAFLD-HCC and their interaction will be realized by evaluating the interaction with risk factors and developing a score to predict NAFLD-HCC. These elements will enable us to select patients for whom screening can be effective.

  up to 84 months

Study Arms (1)

Risk factors for NAFLD-HCC

EXPERIMENTAL

The study will be divided into: * In the first phase, the impact of a score based on the evaluation of common genetic variants in genes predisposing to the development of NAFLD-HCC (PNPLA3, TM6SF2, and MBOAT7), and rare mutations determining high risk of NAFLD-HCC, e.g. . in genes involved in telomere shortening (TERT) and lipid metabolism (APOB) on the risk of developing HCC and on survival, in the entire cohort of patients and in the individual groups listed above. * In the second phase we will use next generation sequencing techniques (whole exome / genome sequencing) to identify new genetic risk variants for the development of HCC.

Other: quantify the impact of genetic risk factors

Interventions

quantify the impact of genetic risk factors OTHER

the impact of genetic risk factors for the development of NAFLD-HCC and their interaction with acquired risk factors, on the incidence of the disease in a prospective cohort of patients at risk, through a score capable of predicting NAFLD-HCC and selecting patients for whom screening is cost-effective.

Risk factors for NAFLD-HCC

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of NAFLD or cryptogenic liver disease, allowing a more liberal alcohol intake limit (\<60/40 g/day in M/F), so as to also include subjects with a moderate alcoholic component of liver disease, an important factor given the high epidemiological burden of this group
• Age between 45 and 75 years
• Any of the following criteria:
• F3-F4 fibrosis, determined histologically, or by non-invasive techniques (stiffness \> 7.9 kPa at Fibroscan and positivity at the NAFLD fibrosis score or at APRI or at FIB4), or evidence of cirrhosis deriving from biochemical tests or imaging methods;
• Family history of primary liver cancer in first degree parentage, or carrier status of rare mutations associated with the development of HCC (such as mutations in APOB and TERT)
• Male patient with type 2 diabetes or obesity carrying at least three genetic variants in PNPLA3, TM6SF2, MBOAT7.
• Willingness to sign the informed consent.

You may not qualify if:

• Alcohol intake \>60/40 g/day in M/F
• Chronic viral or autoimmune hepatitis
• Any previously diagnosed genetic liver disease associated with increased risk of HCC (such as hereditary hemochromatosis, Wilson's disease, Alpha-1 Antitrypsin deficiency)
• Use of drugs known to induce steatosis and liver disease
• HCC diagnosed before the study start date.
• Other pathological conditions with a prognosis of less than two years.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica

Milan, Milano, 20122, Italy

RECRUITING

MeSH Terms

Conditions

Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Luca Vittorio Carlo Valenti

CONTACT

02 5503 6595; luca.valenti@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: July 26, 2024
• Study Start: January 1, 2018
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): December 31, 2035
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

IT (1)