Cirrhosis, Hepatocellular Carcinoma (HCC)
Conditions
Keywords
Screening for HCC in compensated non-viral cirrhosis, HCC surveillance, HCC screening
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTUltrasound of the liver and blood sample for alpha-fetoprotein
Ultrasound of the liver without Doppler or contrast. Alpha-fetoprotein ≥20 \* 10\^3 IE/l, doubling since last measurement or two consecutive increasing measurements.
Sponsors
University of Aarhus
Gødstrup Hospital
Regionshospitalet Horsens
Randers Regional Hospital
Viborg Regional Hospital
Regionshospitalet Silkeborg
Aarhus University Hospital Skejby
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Cirrhosis * No history of chronic hepatitis B or C * Compensated cirrhosis defined as: * No recent variceal bleeding, no uncontrolled ascites, no clinically apparent hepatic encephalopathy, and Child-Pugh score ≤ 8 * 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
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HCC-related mortality | From date of inclusion until death due to hepatocellular carcinoma or end of follow-up, assessed up to 30 months | HCC recorded as the underlying cause of death in the Danish Cause of Death Registry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCC incidence | From date of inclusion until diagnosis of hepatocellular carcinoma or end of follow-up, assessed up to 30 months. | 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. |
| All-cause mortality | From date of first screening to first occurrence of death from any cause assessed up to 30 months. | Survival time based on information from the Danish Central Office of Civil Registration. |
| Use of diagnostic tests | From date of inclusion to first occurrence of death from any cause or diagnosis of hepatocellular carcinoma, assessed up to 30 months. | 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 |
| HCC-related mortality (sensitivity analysis) | From date of first screening to first occurrence of death from hepatocellular carcinoma, assessed up to 30 months. | HCC recorded anywhere on the death certificate (immediate, underlying, or contributory cause) in the Danish Cause of Death Registry. |
Countries
Denmark
Contacts
CONTACTPeter Jepsen, Professor, MD, PhD
CONTACTMorten Hallengreen, PhD student
Outcome results
None listed