The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers.
BACKGROUND
Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers.


METHODS
A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case-control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses.


RESULTS
The final model involving gender, age, AFP-L3, α fetoprotein (AFP), and des-carboxy-prothrombin ("GALAD") was developed in a "discovery" data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage.


CONCLUSIONS
The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches.


CONCLUSIONS
Our data provide evidence that an entirely objective serum biomarker-based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches.
Authors' Affiliations: School of Cancer Sciences; Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham; Department of Molecular and Clinical Cancer Medicine; Liverpool Cancer Research UK Centre, Liverpool Cancer Trials Unit, University of Liverpool, Liverpool; Northern Institute for Cancer Research, Newcastle University; Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; and Wako Life Sciences, Inc., Mountain View, California.
Philip J
PJ
Johnson
Sarah J
SJ
Pirrie
Trevor F
TF
Cox
Sarah
S
Berhane
Mabel
M
Teng
Daniel
D
Palmer
Janet
J
Morse
Diana
D
Hull
Gillian
G
Patman
Chiaki
C
Kagebayashi
Syed
S
Hussain
Janine
J
Graham
Helen
H
Reeves
Shinji
S
Satomura
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor