HCC Risk and Monitoring in Patients With Type 2 Diabetes

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.

Sex

All

Minimum age

18 Years

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).