Digitalized Surveillance Management for Liver Cancer Risk Population in Improving Eearly Diagnosis Efficancy in Chinese Population (dSEARCH)

Study Overview
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Brief Summary
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The goal of this study is to evaluate whether the standardized liver cancer risk stratification management can effectively improve the early diagnosis rate of liver cancer in the targeted risk population in China.

Official Title
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Exploration of A Holistic Management Procedure for Liver Cancer Surveillance in Improving Liver Cancer's Early Diagnosis Efficacy in Chinese Population: Single-Center, Prospective, Observational Real-world Study in EASTERN China

Conditions
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Carcinoma, Hepatocellular, Hepatitis C, Chronic, Hepatitis B, Chronic, Cirrhosis, Liver, Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Behavioral: Liver cancer surveillance every 3 months
* Behavioral: Liver cancer surveillance every 6 months
* Behavioral: Liver cancer surveillance annually


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary participation in the clinical study; fully informed about the study and signed informed consent, willing to follow and capable of completing all trial procedures[17] Age: 18 to 75 years old (including the cut-offs) Subjects must meet at least one of the following criteria for enrollment. Patients diagnosed with chronic hepatitis B in hospital or out of hospital: persistent positive hepatitis B surface antigen (HBsAg) for 6 months or more Patients diagnosed with hepatitis C in hospital or out of hospital Patients diagnosed with cirrhosis in hospital or out of hospital who meet at least one of the following criteria. Liver biopsy showing cirrhosis (Ishak score ≥5 or Metavir score = 4); Liver stiffness measurement (LSM) using FibroScan® (Echosens™, Paris, France) ≥12.0 kPa when TB was normal and ALT ≤ 40 IU/mL, or LSM ≥ 17.0 kPa when TB was normal and ALT < 200 IU/mL; Abdominal imaging results showing characteristic of cirrhosis (results showing coarse liver echotexture or nodular, parenchymal, or morphological abnormalities and signs of gastroesophageal varices); APRI ≥ 2.0; FIB-4 ≥ 3.25 Patients diagnosed with metabolic dysfunction-associated fatty liver disease (MAFLD) in hospital or out of hospital who have a liver fibrosis score of F3 or higher according to transient elastography, i.e., FibroScan® Liver Stiffness Measurement (LSM) ≥ 10 kPa or the corresponding FibroTouch® measurement threshold[18]. MAFLD diagnosis requires diagnosis of >5% fat accumulation in liver through either FibroScan® CAP measurements, or similar parameter, or liver biopsy, and in combination with one of the following three conditions: overweight/obesity (BMI >23 kg/m2), type 2 diabetes, or metabolic dysfunction. Patients diagnosed with MAFLD combined with abnormal glucose metabolism[19] Abnormal glucose metabolism is defined as type 2 diabetes, or prediabetes, i.e. fasting blood glucose 5.6-6.9 mmol/L, or 2h postprandial blood glucose 7.8-11.0 mmol/L, or glycated hemoglobin 5.7%-6.4% Subjects with a family history of liver cancer in their first-degree biological relatives. Exclusion Criteria: Patients meeting any of the following criteria will be excluded from the study: Age <18 years or >75 years Patients who have been diagnosed with liver cancer before enrollment Patients with severe mental illness or cognitive impairment Patients who are pregnant or lactating, or preparing to become pregnant Patients who have participated in other clinical trials or are participating in other clinical trials within 3 months prior to initiation of study treatment According to the doctor's judgment, the possibility of the subject being included is low (including inability to understand the project requirements , poor compliance, infirmity, inability to ensure that the protocol can be implemented as required, etc.), or the doctor determines that the subject has any other factors that are not suitable for this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with very high risk for HCC according local guideline<br> | Behavioral: Liver cancer surveillance every 3 months<br>* Follow up every 3 months for liver cancer surveillance, including but not limited to serum AFP test and ultrasound exam<br>|
| Patients with high risk for HCC according local guideline<br> | Behavioral: Liver cancer surveillance every 3 months<br>* Follow up every 3 months for liver cancer surveillance, including but not limited to serum AFP test and ultrasound exam<br>|
| Patients with medium risk for HCC according local guideline<br> | Behavioral: Liver cancer surveillance every 6 months<br>* Follow up every 6 months for liver cancer surveillance, including but not limited to serum AFP test and ultrasound exam<br>|
| Patients with low risk for HCC according local guideline<br> | Behavioral: Liver cancer surveillance annually<br>* Follow up annually for liver cancer surveillance, including but not limited to serum AFP test and ultrasound exam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early diagnosis rate of HCC patients | The proportion of patients who are first diagnosed with HCC at early stage to all the patients diagnosed as liver cancer in the study, from the start of the study to the completion of follow-up. Early diagnosis is defined as the patient with stage CNLC Ia, Ib and IIa. | Follow up up to three years for HCC occurance. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with regular follow-up | Regular follow-up is defined as the average difference between the actual treatment time and the theoretical treatment time equal or less than 1/3 Actual visit interval: actual visit date - previous visit date ② Theoretical visit interval: theoretical visit date (the date that physician advise to return to hospital for visit) - previous visit date ③ Follow-up compliance = (②-①)/② ④ Patient with regular follow-up is defined as the patient whose mean follow-up compliance is equal to, or less than 1/3 The compliance of the study is defined as the proportion of subjects with regular follow-up to all subjects in the study. | Four years collectively after the study started | 
| The distribution of risk stratification of liver cancer in subjects at initial screening | The proportion of very high-risk, high-risk, medium-risk, and low-risk subjects to the whole subject population | Initial screening after enrollment | 
| The distribution of risk stratification of liver cancer in subjects at the last follow-up visit or at the time of diagnosis of liver cancer | The proportion of very high-risk, high-risk, medium-risk and low-risk subjects to the whole subject population | Last follow-up visit or at the time of diagnosis of liver cancer up to three years of follow-up | 
| Pooled 3-year cumulative incidence of liver cancer |  | Follow up up to 3 years | 
| The early diagnosis rate of liver cancer in each subject category according to the risk stratification at initial screening | The early diagnosis rate of liver cancer of subjects with very high-risk, high-risk, medium-risk, and low-risk at initial screening, respectively | Initial screening after enrollment | 
| The 3-year cumulative incidence of liver cancer in each subject category according to the risk stratification at the time of initial diagnosis | The 3-year cumulative incidence of liver cancer for subjects with very high-risk, high-risk, medium-risk, and low-risk, respectively | Four years collectively after the study started |