Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Biomarkers, Tumor/*genetics ; Carcinoma, Hepatocellular/*diagnosis ; Early Detection of Cancer/*methods ; Hepatitis C/*diagnosis ; Liver Cirrhosis/*diagnosis ; Liver Neoplasms/*diagnosis ; alpha-Fetoproteins/*genetics; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/genetics ; Female ; Hepatitis C/complications ; Hepatitis C/epidemiology ; Hepatitis C/genetics ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/epidemiology ; Liver Cirrhosis/genetics ; Liver Neoplasms/epidemiology ; Liver Neoplasms/etiology ; Liver Neoplasms/genetics ; Male ; Middle Aged ; Public Health Surveillance/methods ; Survival Analysis ; Ultrasonography ; United Kingdom/epidemiology ; alpha-Fetoproteins/metabolism

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.

Lancet Oncol. 2009 Nov;10(11):1111-8. (PMID: 19880065)
Hepatology. 2011 Mar;53(3):1020-2. (PMID: 21374666)
Am J Gastroenterol. 2004 Aug;99(8):1470-6. (PMID: 15307862)
Ann Intern Med. 2003 Jul 1;139(1):46-50. (PMID: 12834318)
Hepatology. 2002 Aug;36(2):410-7. (PMID: 12143050)
Clin Gastroenterol Hepatol. 2012 Apr;10(4):428-33. (PMID: 22155556)
Clin Gastroenterol Hepatol. 2015 Apr;13(4):799-804. (PMID: 25117773)
J Hepatol. 2015 Nov;63(5):1156-63. (PMID: 26100498)
J Gastroenterol Hepatol. 2007 May;22(5):669-75. (PMID: 17444854)
Am J Gastroenterol. 2006 Mar;101(3):524-32. (PMID: 16542289)
Hepatogastroenterology. 2015 Mar-Apr;62(138):327-32. (PMID: 25916058)
Gastroenterology. 2012 Oct;143(4):986-94.e3; quiz e14-5. (PMID: 22750200)
Liver Int. 2015 Jan;35(1):232-9. (PMID: 24576055)
Br J Cancer. 2015 Jan 6;112(1):69-76. (PMID: 25314061)
Aliment Pharmacol Ther. 2009 Jul;30(1):37-47. (PMID: 19392863)
Hepatogastroenterology. 2012 May;59(115):840-3. (PMID: 22469729)
Hepatology. 2012 Oct;56(4):1371-9. (PMID: 22535689)
Clin Gastroenterol Hepatol. 2015 Apr;13(4):791-8.e1. (PMID: 25019694)
Dig Dis Sci. 2014 Dec;59(12 ):3073-7. (PMID: 25027206)
Hepatology. 2000 Oct;32(4 Pt 1):842-6. (PMID: 11003632)
Clin Gastroenterol Hepatol. 2016 Mar;14 (3):469-475.e2. (PMID: 26260109)
Cancer Res. 2009 Sep 15;69(18):7385-92. (PMID: 19723656)
World J Surg Oncol. 2013 Aug 27;11:212. (PMID: 23981851)
Cancer. 2014 Sep 15;120(18):2824-38. (PMID: 24897995)
Am J Gastroenterol. 2013 Mar;108(3):425-32. (PMID: 23337478)
Dig Dis Sci. 2011 May;56(5):1516-23. (PMID: 21046247)
PLoS One. 2012;7(12):e50919. (PMID: 23236406)
J Cancer Res Clin Oncol. 2004 Jul;130(7):417-22. (PMID: 15042359)
Clin Gastroenterol Hepatol. 2013 Apr;11(4):441-3. (PMID: 23376321)
Am J Gastroenterol. 2015 Jun;110(6):836-44; quiz 845. (PMID: 25869392)
Hepatology. 2014 Mar;59(3):986-95. (PMID: 24123097)
J Viral Hepat. 2008 Mar;15(3):179-87. (PMID: 18233991)
Am J Gastroenterol. 2006 Mar;101(3):513-23. (PMID: 16542288)
Clin Gastroenterol Hepatol. 2013 Apr;11(4):437-40. (PMID: 23247324)
PLoS Med. 2014 Apr 01;11(4):e1001624. (PMID: 24691105)
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. (PMID: 21296855)
Hepatology. 2005 Nov;42(5):1208-36. (PMID: 16250051)
J Surg Oncol. 2014 Dec;110(8):967-9. (PMID: 25155168)
J Hepatol. 2012 Apr;56(4):908-43. (PMID: 22424438)
Gastroenterology. 2010 Feb;138(2):493-502. (PMID: 19852963)

United Kingdom WT_ Wellcome Trust; MC_U105260558 United Kingdom MRC_ Medical Research Council; MC_U105260794 United Kingdom MRC_ Medical Research Council

0 (Biomarkers, Tumor)
0 (alpha-Fetoproteins)

Date Created: 20160617 Date Completed: 20170712 Latest Revision: 20220129

20221213

PMC4911090

10.1371/journal.pone.0156801

27308823