Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.
Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance.
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.|Cancer Research UK Beatson Institute, Glasgow, G61 1BD, United Kingdom.
Thomas G
http://orcid.org/0000-0002-6120-1581
TG
Bird
MRC Biostatistics Unit, Cambridge, CB2 0SR, United Kingdom.
Polyxeni
P
Dimitropoulou
MRC Biostatistics Unit, Cambridge, CB2 0SR, United Kingdom.
Rebecca M
RM
Turner
Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Sara J
SJ
Jenks
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Pearce
http://orcid.org/0000-0003-1879-274X
P
Cusack
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Shiying
S
Hey
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Andrew
A
Blunsum
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Sarah
S
Kelly
Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Catharine
C
Sturgeon
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, United Kingdom.
Peter C
PC
Hayes
MRC Biostatistics Unit, Cambridge, CB2 0SR, United Kingdom.|Department of Mathematics and Statistics, Strathclyde University, Glasgow, G1 1XH, United Kingdom.
Sheila M
SM
Bird
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D062486:Public Health Surveillance / Q000379:methods; D016019:Survival Analysis; D014463:Ultrasonography; D006113:United Kingdom / Q000453:epidemiology; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins