A validation study of des-gamma carboxy-prothrombin for the detection of early hepatocellular carcinoma

Aim

To develop better biomarkers for the early detection of hepatocellular carcinoma (HCC).

Inclusion Criteria

A. HCC Cases

Age >18 years of age
Diagnosis of HCC will be based on the following:
-Histology
-2 imaging tests (CT/MRI/Angiography) showing a vascular lesion of >2 cm
-AFP >400 ng/mL and a vascular lesion on 1 imaging test (CT/MRI/Angiography)

B. Controls

Age >18 years of age
Diagnosis of cirrhosis based on imaging showing a cirrhotic-appearing liver with splenomegaly and a platelet count of <120 kmm -3
Normal ultrasound or other imaging within 6 months of enrollment
Patients with AFP >20 ng/mL will be included if MRI or CT scan within 3 months prior to enrollment revealed no mass suggestive of HCC

Exclusion Criteria

Prior treatment of HCC (for cases)
Clinical evidence of significant hepatic decompensation (for controls)
Detection of HCC at initial evaluation (for controls)

Study Design

Case control study of cirrhotics and HCC
Serum, plasma, and DNA will be obtained

Cirrhotics will be followed for an additional 6 months to assure no HCC.

Please notify of HCC cases: Sherry Fu at (734) 647-3635 (e-mail: sherryfu@umich.edu) or Dr. Jorge A. Marrero at (734) 615-5480 (e-mail: jmarrero@umich.edu )

Prospective evaluation of tumor markers for the early detection of hepatocellular carcinoma

This is an extension of the above study. We plan to follow a cohort of patients with cirrhosis over time to identify the rate of development of hepatocellualr carcinoma (HCC), to validate novel biomarkers, and to stratify cirrhotic patients into high- and low-risk for development of HCC based on their exposures to tobacco, alcohol, obesity, and other factors.

Specific Aims

To determine if serum DCP, GP73, or a combination of these markers is more sensitive than AFP for the detection of early HCC.
To determine if studies of the proteomics of HCC can lead to the development of novel serum markers of early HCC.
To determine if tobacco, alcohol, obesity, demographics, and etiology of liver disease are important factors for the development of HCC in patients with cirrhosis.

Inclusion Criteria

• All adult patients with liver cirrhosis
• Diagnosis of cirrhosis will be based on histology or an ultrasound showing a cirrhotic-appearing liver with splenomegaly and a platelet count of <120 kmm -3
• Child class A or B
• All patients must have normal ultrasond or other imaging within 6 months of enrollment
• Patients with AFP >20 ng/mL will be included if MRI or CT scan within 3 months prior to enrollment revealed no mass suggestive of HCC

Exclusion Criteria

Clinical evidence of significant hepatic decompensation (refractory ascites, grades 3 to 4 encephalopathy, or hepatorenal syndrome), Child class C, or MELD score >15.
Detection of HCC at initial evaluation.
Inability to comply with long-term follow-up
Significant comorbid medical conditions with life expectancy less than 1 year.
Require long-term immunosuppressive therapy.
Prior solid organ transplant.
Primary tumor in an extrahepatic site.

Study Design

• Patients will be seen every 6 months over a 5-year period
• Lifetime alcohol and tobacco questionnaires at baseline
• Clinical and laboratory data will be obtained every 6 months
• Serum, plasma, and DNA obtained every 6 months

Please notify of patients with Child A or B cirrhosis who will be followed long-term: Sherry Fu at (734) 647-3635 (e-mail: sherryfu@umich.edu) or Dr. Jorge A. Marrero at (734) 615-5480 (e-mail: jmarrero@umich.edu )

Diagnosis and Prognosis of Patients with Hepatocellular Carcinoma

Patients with chronic liver disease are at risk of developing Hepatocellular Carcinoma (HCC). This research study will evaluate the potential outcome of patients with liver tumors. This study plans to evaluate the Barcelona staging system in patients with HCC and evaluate if new biomarker at the time of HCC diagnosis improves the accuracy of the Barcelona staging system in predicting the outcome of patients with liver cancer.

Specific Aims

Evaluation of the prognosis of patients with Hepatocellular Carcinoma
To prospectively evaluate the Barcelona staging system in patients with HCC

To determine if novel biomarker expression at the time of HCC diagnosis improves the accuracy of the Barcelona staging system in predicting the prognosis of patients with HCC.

Please notify of HCC cases: Sherry Fu (734) 647-3635 or sherryfu@umich.edu or Dr. Jorge A. Marrero at jmarrero@umich.edu