Screening for Hepatitis Virus B Protein X (HBx) in Colitis-associated Cancer (CAC)

NCT06833021 | Not Yet Recruiting

• 1 other identifier: HBx-CAC
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

It was recently discovered that a protein from the Hepatitis B Virus (HBV), called HBx, is highly present in patients who were recently diagnosed with Ulcerative Colitis (UC). This was more common in UC patients than in healthy individuals or those with Crohn's Disease. About 45% of the UC patients studied had this protein, possibly due to a virus jumping from animals to humans. In experiments with mice, it was found that HBx alone can cause colitis (inflammation of the colon) by disrupting the normal function of the gut lining. This disruption leads to inflammation and immune system problems in the colon, even without other bacteria being involved. Mice treated with HBx showed fewer immune cells, which are crucial for resolving inflammation and fighting infections. This aligns with current theories about how UC develops. Additionally, HBx affects the genes in the gut lining, promoting cell growth and changes that could lead to cancer. In human colon tissue samples, HBx activated processes linked to the Wnt pathway, which is known to be involved in colorectal cancer. This is similar to how HBx behaves in liver cells infected with HBV, where it prevents DNA repair and leads to cancer. Based on these findings, it is believed that HBx disrupts the balance in the gut, causing chronic inflammation that could progress to cancer. To explore this further, a study is being conducted to detect HBx in tissue samples from patients with colitis-associated cancer (CAC). Advanced techniques will be used to analyze these samples and compare them with samples from patients with other conditions like diverticulitis, indeterminate colitis, and Crohn's disease without cancer

Conditions

Colitis-associated Colorectal Cancer (CAC)

Keywords

Colorectal Cancer; Hepatitis Virus B; Hepatitis Virus B Protein X; IBD; Diverticulitis; Colitis; Crohn Disease; Colitis-associated Colorectal Cancer (CAC)

Outcome Measures

Primary Outcomes (1)

• To define HBx as a predictive biomarker of CAC in UC patients

  FFPE tissue blocks from patients diagnosed with CAC, including low- and high-grade dysplasia and adenocarcinoma, obtained from pathological archives will be used. RNA will be extracted and analyzed using RT-PCR to detect and quantify HBx transcripts, with Sanger sequencing employed for further validation of the results. Additionally, FFPE tissue blocks from CRC, diverticulitis, IC and CD without cancer patients will be utilized as controls. FFPE tissue blocks already present in the Pathology Unit will be used.

  Being a retrospective study, we plan to collect FFPE stored from October 2021 to December 2024. Duration of total study period: 12 months.

Study Arms (2)

Control Group

33 patients used as control including patients with CRC not associated with colitis, diverticulitis, IC and CD without cancer.

Other: Transcriptomic Analysis

Case Group

33 patients diagnosed with CAC

Other: Transcriptomic Analysis

Interventions

Transcriptomic Analysis OTHER

FFPE tissue blocks from patients diagnosed with CAC, including low- and high-grade dysplasia and adenocarcinoma, obtained from pathological archives will be used. RNA will be extracted and analyzed using RT-PCR to detect and quantify HBx transcripts, with Sanger sequencing employed for further validation of the results.

Case Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

66 total patients, of which 33 diagnosed with CAC and 33 representing the control group composed of CRC without colitis, diverticulitis, and CD without cancer. 20 patients will be enrolled at our center, and the remaining 40 will be equally distributed among the participating units: IRCCS Casa Sollievo della Sofferenza Hospital (San Giovanni Rotondo (FG), Italy) and Western University (London, Ontario, Canada).

You may qualify if:

• adult patients (age ≥18 years), both male and female, diagnosed with CAC, CRC, diverticulitis, IC or CD who had previously undergone endoscopic biopsy or surgical resection, according to standard clinical practice (from 2021 to 2024);
• patients with no documented history of HBV infection;
• patients who had already signed the informed consent authorizing the use of their clinical data for future scientific research.

You may not qualify if:

• patients under 18 years of age;
• adult patients (age ≥18 years), both male and female diagnosed with CAC, CRC, diverticulitis, IC or CD with a documented history of HBV infection;
• patients who have not signed the informed consent authorizing the use of their clinical data for future scientific research.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo: collaborator
• Western University, Canada: collaborator

Study Sites (1)

IRCCS San Raffaele

Milan, Italy, 20132, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

FFPE tissue from endoscopic biopsies or surgical resection

MeSH Terms

Conditions

Colitis-Associated Neoplasms; Colorectal Neoplasms; Diverticulitis; Colitis; Crohn Disease

Condition Hierarchy (Ancestors)

Colonic Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Diverticular Diseases; Gastroenteritis; Inflammatory Bowel Diseases

Study Officials

• Silvio Danese, PhD-MD

  IRCCS San Raffaele

  STUDY DIRECTOR

Central Study Contacts

Silvio Danese, PhD.-MD

CONTACT

+39 0226432807; danese.silvio@hsr.it

Federica Ungaro, PhD.

CONTACT

+39 0226437864; ungaro.federica@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: February 18, 2025
• Study Start: April 1, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

IT (1)