Hepatocellular Carcinoma (HCC), Type 2 Diabetes (T2DM)
Conditions
Keywords
Type 2 Diabetes, Liver Cancer, Surveillance, Prospective Randomized Study
Brief summary
Liver cancer is a significant malignancy in Taiwan. With the widespread implementation of antiviral therapies, hepatitis B and C-related liver cancer has gradually declined; however, metabolic dysfunction-associated liver cancer continues to increase, particularly among patients with type 2 diabetes mellitus (T2DM) who also present with significant liver fibrosis. Current clinical guidelines lack standardized recommendations for liver cancer screening in this specific population, and data from prospective randomized controlled trials remain scarce.This study is a prospective randomized controlled trial enrolling patients aged 18 years, diagnosed with T2DM, and with a FIB-4 \> 2.67. Participants will be randomly assigned to either the surveillance group or the standard-care group. The surveillance group will undergo blood tests every 6 months to monitor liver function, AFP, and PIVKA-II, alongside the calculation of the GAAD score. The standard-care group will receive liver function tests every 6 months according to routine clinical practice. Abdominal ultrasound or computed tomography (CT) scans will be arranged by clinicians when clinically indicated. All participants will undergo abdominal ultrasound at baseline and at the end of the third year, with blood samples and clinical data collected periodically. The primary endpoint of this study is the tumor size at the time of liver cancer diagnosis. Secondary endpoints include liver cancer staging, number of liver cancer tumors, liver cancer incidence, the proportion of patients receiving curative treatment, and the degree of liver fibrosis as reflected by changes in FIB-4. This study expects to clarify the clinical benefits of a GAAD score-based surveillance strategy compared to standard care in T2DM patients with high FIB-4 scores, thereby providing evidence-based support for future liver cancer screening strategies and clinical guidelines.
Interventions
DIAGNOSTIC_TESTGAAD score
GAAD score (Gender, age, AFP, DC) will be measured every 6 months in the GAAD Surveillance Group.
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * Diagnosed with type 2 diabetes mellitus and clinically followed with regular outpatient visits. * FIB-4 index greater than 2.67 (calculated based on AST, ALT, and platelet count within the past 6 months). * Willing and able to provide written informed consent.
Exclusion criteria
* HBsAg positive. * Anti-HCV positive and HCV RNA positive (patients with anti-HCV positive but negative HCV RNA are still eligible). * Prior history of hepatobiliary malignancies. * Undergoing regular abdominal ultrasound screening more than once per year. * Established diagnosis of liver cirrhosis via abdominal ultrasound or clinical evaluation. * Diagnosed with or treated for any malignancy within the past 2 years. * Women of childbearing potential or pregnant women. * Thrombocytopenia secondary to hematologic disorders. * Known history of human immunodeficiency virus (HIV) infection. * Concomitant use of medications that may interfere with PIVKA-II assay results (e.g., warfarin, vitamin K).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tumor diameter of hepatocellular carcinoma (cm). | From the date of enrollment up to 3 years. | The maximal tumor diameter of all HCC tumors, measured in centimeters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage of hepatocellular carcinoma. | From the date of enrollment up to 3 years. | The stage of HCC, using the BCLC staging and the AJCC TNM staging |
| Number of hepatocellular carcinoma tumors | From the date of enrollment up to 3 years | The number of HCC tumors evaluated by abdominal CT or MRI exams |
| Incidence of hepatocellular carcinoma | From the date of enrollment up to 3 years | The rate of new HCC developed during the study |
| Proportion of hepatocellular carcinoma cases receiving curative treatment. | From the date of enrollment up to 3 years. | Proportion of hepatocellular carcinoma cases receiving curative treatment (including liver transplantation, surgical resection, local ablation, proton therapy, and etc.) |
| Changes in the degree of liver fibrosis as assessed by the FIB-4 index. | From the date of enrollment up to 3 years. | The serial FIB-4 level changes during the study period (measured every 6 months) |
| Participant return-visit rate (adherence to trial follow-up). | From the date of enrollment up to 3 years. | The rate of patients who adhere to trial follow-up. Calculated by number of visits divided by total number of planned visits. |
| Incidence of liver cirrhosis. | From the date of enrollment up to 3 years. | The number of participants who developed liver cirrhosis (diagnosed by FibroScan \> 15 kPa, or a clinical diagnosis by ultrasound, CR, or MRI). |
| Number of computed tomography (CT) or magnetic resonance imaging (MRI) examinations performed for the purpose of hepatocellular carcinoma screening. | From the date of enrollment up to 3 years. | The total number of computed tomography (CT) or magnetic resonance imaging (MRI) examinations performed for the purpose of hepatocellular carcinoma screening during the study period. |
Countries
Taiwan
Contacts
CONTACTTung-Hung Su, PhD
PRINCIPAL_INVESTIGATORTung-Hung Su, MD, PhD
National Taiwan University Hospital
Outcome results
None listed