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| Name | Class |
|---|---|
| Gødstrup Hospital | OTHER |
| Regionshospitalet Horsens | OTHER |
| Randers Regional Hospital | OTHER |
| Viborg Regional Hospital |
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This study aims to investigate whether repeated 6-monthly screening for hepatocellular carcinoma (HCC) - called "HCC surveillance" - offered to selected patients with chronic liver disease can reduce HCC-related mortality by facilitating earlier detection of HCC. The screening procedure consists of two tests: an ultrasound examination of the liver and a blood sample to measure alpha-fetoprotein. Patients who screen positive on either examination will be offered standard work-up for HCC, typically beginning with a CT-scan.
In the study HCC surveillance will be offered to all patients with compensated non-viral cirrhosis residing in the Central Denmark Region, one of five administrative regions of Denmark. The study aims to determine the efficacy of HCC surveillance in reducing HCC-related mortality by comparing HCC-related mortality between the Central Denmark Region and the other four Danish regions, where HCC surveillance is not offered.
Primary liver cancer is the sixth most common cancer and the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and often develops in patients with chronic liver disease (cirrhosis), who have a substantially increased risk of HCC.
Because of this high risk, repeated screening for HCC, commonly referred to as HCC surveillance, is recommended by all major international liver societies. The hope is to identify HCC while curative treatment is still possible. In Denmark, HCC surveillance is only recommended for patients with cirrhosis caused by chronic viral hepatitis. Currently, it is not recommended to other patients with cirrhosis due to these patients' low risk of HCC and the lack of randomized studies to determine the efficacy of HCC surveillance as a means to reduce HCC-related or all-cause mortality.
On the study HCC surveillance is introduced for patients with compensated non-viral cirrhosis in the Central Denmark Region, one of Denmark's five administrative regions. Screening will consist of biannual abdominal ultrasound combined with alpha-fetoprotein (AFP) testing. Patients who screen positive will be offered standard work-up for HCC. 600 patients are expected to be enrolled and they will be offered three rounds of screening at 0, 6 months, and 12 months, i.e., there is no individual-level randomization in this study. Instead, national registry data will be used to compare HCC-related mortality (the primary outcome) and HCC incidence and other secondary outcomes between the Central Denmark Region and the other four Danish regions where HCC surveillance is not offered.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Assigned to HCC surveillance using 6-monthly abdominal ultrasound and alpha-fetoprotein | Experimental |
| |
| Assigned to standard of care | No Intervention | These patients are not followed within the study. Instead, patients in the target population from other regions in Denmark-who are comparable to those receiving the intervention-will serve as the comparison group. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ultrasound of the liver and blood sample for alpha-fetoprotein | Diagnostic Test | Ultrasound of the liver without Doppler or contrast. Alpha-fetoprotein ≥20 * 10^3 IE/l, doubling since last measurement or two consecutive increasing measurements. |
| Measure | Description | Time Frame |
|---|---|---|
| HCC-related mortality | HCC recorded as the underlying cause of death in the Danish Cause of Death Registry. | From date of inclusion until death due to hepatocellular carcinoma or end of follow-up, assessed up to 30 months |
| Measure | Description | Time Frame |
|---|---|---|
| HCC incidence | Incidence of HCC determined a diagnosis code for HCC (ICD-10: C22.0) recorded in the Danish Cancer Register and/or as a primary diagnosis code in the Danish National Patient Register. | From date of inclusion until diagnosis of hepatocellular carcinoma or end of follow-up, assessed up to 30 months. |
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Inclusion Criteria:
Cirrhosis
No history of chronic hepatitis B or C
Compensated cirrhosis defined as:
Age 40-79 years
Expected remaining life expectancy ≥ 1 year
Not already in follow-up after treatment for HCC
No clinical suspicion of HCC
Exclusion Criteria:
-
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Peter Jepsen, Professor, MD, PhD | Contact | +45 29314466 | pj@clin.au.dk | |
| Morten Hallengreen, PhD student | Contact | +45 60154398 | mohall@clin.au.dk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Recruiting | Aarhus | Central Jutland | 8200 | Denmark |
Our study design implies that we have no contact with the population offered the standard-of-care, who will be identified through the Danish healthcare registers. Moreover, all outcome information will be collected through the Danish healthcare registers. We will only be allowed access to these healthcare registers through a remote server in a Trusted Research Environment (TRE). Danish law prohibits us from downloading, let alone sharing, data from the TRE.
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| OTHER |
| Regionshospitalet Silkeborg | OTHER |
| Aarhus University Hospital Skejby | OTHER |
Patients enrolled in the Central Denmark Region will receive the intervention. They will then be compared to patients from the other Danish Regions who receive the standard of care.
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| All-cause mortality |
Survival time based on information from the Danish Central Office of Civil Registration. |
| From date of first screening to first occurrence of death from any cause assessed up to 30 months. |
| Use of diagnostic tests | This includes: Alpha-fetoprotein Ultrasound of the liver CT of the liver, including 3-phase or 4-phase liver CT MR of the liver Liver biopsy for HCC | From date of inclusion to first occurrence of death from any cause or diagnosis of hepatocellular carcinoma, assessed up to 30 months. |
| HCC-related mortality (sensitivity analysis) | HCC recorded anywhere on the death certificate (immediate, underlying, or contributory cause) in the Danish Cause of Death Registry. | From date of first screening to first occurrence of death from hepatocellular carcinoma, assessed up to 30 months. |
| Regional Hospital Gødstrup | Recruiting | Herning | Central Jutland | 7400 | Denmark |
|
| Horsens Regional Hospital | Recruiting | Horsens | Central Jutland | 8700 | Denmark |
|
| Randers Regional Hospital | Recruiting | Randers | Central Jutland | 8930 | Denmark |
|
| Silkeborg Regional Hospital | Recruiting | Silkeborg | Central Jutland | 8600 | Denmark |
|
| Viborg Regional Hospital | Recruiting | Viborg | Central Jutland | 8800 | Denmark |
|
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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