The association of AFP, AST, ALT and Neutrophil to lymphocyte ratio for diagnosis hepatocellular carcinoma

Authors

  • Yaninee Jarratwisarutporn Department of Clinical Pathology and Medical Technology, National Cancer Institute
  • Vichuda Triratatichart Department of Clinical Pathology and Medical Technology, National Cancer Institute
  • Maneerut Mus-u-dee Department of Clinical Pathology, National Cancer Institute

Keywords:

Hepatocellular carcinoma (HCC), Alpha-fetoprotein (AFP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), neutrophil to lymphocyte ratio (NLR)

Abstract

Alpha-fetoprotein (AFP) is a tumor marker widely used in the diagnosis and monitoring of hepatocellular carcinoma (HCC). However, it is not applicable to the diagnosis of HCC in all individuals due to the possibility that some liver cancer patients may have AFP levels within the reference range. Elevated levels of AFP have also been found in patients with other liver diseases. Based on this limitation, our study aimed to investigate the combination of routine blood examinations, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and neutrophil to lymphocyte ratio (NLR), with AFP to increase sensitivity and specificity in diagnosing HCC compared to other liver diseases. This research is a retrospective descriptive study. Data were collected from patients diagnosed with HCC and liver diseases, treated at the National Cancer Institute from January 1, 2019 to December 31, 2022. Results: In total, 203 patients were included, with 96 had HCC and 107 had liver diseases. The area under the ROC curve for HCC diagnosis of AFP, ALT, AST, and NLR were 0.77 (0.72–0.82), 0.70 (0.64–0.76), 0.62 (0.55–0.69), and 0.57 (0.51–0.64) with optimum cut-off values of 20.7 ng/mL, 26 IU/mL, 27 IU/mL and 1.724, respectively. Of all four cut-off values, AST had the highest diagnosing sensitivity for HCC at 83.3%, but with relatively low specificity (57%). AFP had the highest specificity for diagnosing HCC at 98.1%, but the lowest sensitivity at 55.2%. when used together, the combination of AFP and AST showed the highest area under the ROC curve values of 0.74 (0.68-0.79), with sensitivity at 49% and specificity at 98.1%, albeit with reduced sensitivity compared to AFP or AST alone. In patients with AFP levels below 20 ng/mL, AST also showed the maximum area under the ROC curve of 0.67 (0.59-0.75). In conclusion, the HCC diagnostic values of AFP, AST, ALT, and NLR, as well as the combined correlation analyzed from the data, demonstrate that AFP remains a good diagnostic marker for HCC. Although it exhibits relatively low sensitivity, it has very high specificity. AST aids in increasing sensitivity in the diagnosis of HCC.

References

International Agency for Research on Cancer [Internet] : Cancer fact sheets; 2020 [cited 2022 May 23].

Available from: https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf

International Agency for Research on Cancer [Internet] : Cancer fact sheets; 2020 [cited 2022 May 23].

Available from: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf

International Agency for Research on Cancer [Internet]: Population fact sheets; 2020 [cited 2022 May 23].

Available from: https://gco.iarc.fr/today/data/factsheets/populations/764-thailand-fact-sheets.pdf

กองยุทธศาสตร์และแผนงาน สำนักงานปลัดกระทรวงสาธารณสุข.สถิติสาธารณสุข พ.ศ. 2563 [อินเทอร์เน็ต].

[เข้าถึงเมื่อ 25 มิ.ย. 2565].เข้าถึงได้จาก: http://www.pcko.moph.go.th/ Health-Statistics /statis tic2563.pdf

Liu Y, Liu L. Changes in the Epidemiology of Hepatocellular Carcinoma in Asia. Cancers 2022 Sep 15;14(18):4473.

doi: 10.3390/cancers14184473.

McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021 Jan;73

Suppl 1(Suppl 1):4-13. doi: 10.1002/hep.31288.

Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 2000 Dec;15(12):1356-61. doi:10.1046/j.1440-1746.2000.0150121356.x.

Dimitroulis D, Damaskos C, Valsami S, Davakis S, Garmpis N, Spartalis E, et al. From diagnosis to treatment of hepatocellular

carcinoma: An epidemic problem for both developed and developing world. World J Gastroenterol. 2017 Aug 7;23(29):5282-5294.

doi: 10.3748/wjg.v23.i29.5282.

Wang J., Zhang P., Liao J., Zhu Y., Liu X., Tang H. Association of α-fetoprotein levels with liver stiffness measurement

in outpatients with chronic hepatitis B. Biosci Rep. 2021 Jan 29;41(1):BSR20203048. doi: 10.1042/BSR20203048.

Manuc D, Preda CM, Sandra I, Baicus C, Cerban R, Constantinescu I, et al. Signification of Serum Alpha-Fetoprotein

Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma. J Med Life.

Jan-Mar;13(1):68-74. doi: 10.25122/jml-2019-0076.

El-Serag, H.B.; Kanwal, F.; Davila, J.A.; Kramer, J.; Richardson, P. A New Laboratory-Based Algorithm to Predict

Development of Hepatocellular Carcinoma in Patients with Hepatitis C and Cirrhosis. Gastroenterology 2014;146:1249–55.

Liu YR, Lin BB, Zeng DW, et al. Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional

study of 619 consecutive patients with chronic hepatitis B. BMC Gastroenterol 2014;14:145.

Manuc D, Preda CM, Sandra I, Baicus C, Cerban R, Constantinescu I, et al. Signification of Serum Alpha-Fetoprotein Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma. J Med Life. 2020 Jan-Mar;13(1):68-74.

doi: 10.25122/jml-2019-0076.

Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020, 360 (2020). https://doi.org/10.1186/s12916-020-01817-1

Hu J, Wang N, Yang Y, Ma L, Han R, Zhang W, et al. Diagnostic value of alpha-fetoprotein combined with neutrophil-

to-lymphocyte ratio for hepatocellular carcinoma. BMC Gastroenterology. 2018; 18: 186.

สมาคมโรคตับแห่งประเทศไทย. แนวทางการดูแลผู้ป่วยมะเร็งตับในประเทศไทย ปี พ.ศ. 2564 (ฉบับปรับปรุง).[อินเทอร์เน็ต].

[เข้าถึงเมื่อ 10 เมษายน 2564]. เข้าถึงได้จาก: https://thasl.org/แนวทางการดูแลมะเร็งตับในประเทศไทย-พ-ศ-2564/

Liu X, Meng J, Xu H, Niu J. Alpha-fetoprotein to transaminase ratio is related to higher diagnosis

efficacy for hepatocellular Carcinoma. Medicine 2019; 98: 17.e15414.

Jang ES, Jeong SH, Kim JW, Choi YS, Leissner P, Brechot C. Diagnostic Performance of Alpha-Fetoprotein, Protein Induced

by Vitamin K Absence, Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma. PLOS One. 2016; 11(3): e0151069.

Chimparlee N, Chuaypen N, Khlaiphuengsin A, Pinjaroen N, Payungporn S, Poovorawan Y, et al. Diagnostic and Prognostic

Roles of Serum Osteopontin and Osteopontin Promoter Polymorphisms in Hepatitis B-related Hepatocellular Carcinoma. APJCP. 2015;16(16):7211–7. doi: 10.7314/apjcp.2015.16.16.7211.

Lee CW, Tsai HI, Lee WC, Huang SW, Lin CY, Hsieh YC, Kuo T, Chen CW, Yu MC. Normal Alpha-Fetoprotein Hepatocellular

Carcinoma: Are They Really Normal? J Clin Med. 2019 Oct 19;8(10):1736. doi: 10.3390/jcm8101736

Ahn DG, Kim HJ, Kang H, Lee HW, Bae SH, Lee JH, Paik YH, Lee JS. Feasibility of α-fetoprotein as a diagnostic tool for

hepatocellular carcinoma in Korea. Korean J Intern Med. 2016 Jan;31(1):46-53. doi: 10.3904/kjim.2016.31.1.46.

Choi J, Kim GA, Han S, Lee W, Chun S, Lim YS. Longitudinal Assessment of Three Serum Biomarkers to Detect Very Early-Stage Hepatocellular Carcinoma. Hepatology. 2019;69(5):1983-94. doi: 10.1002/hep.30233.

Guan MC, Wang MD, Liu SY, Ouyang W, Liang L, Pawlik TM, Xu QR, Huang DS, Shen F, Zhu H, Yang T. Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside. World J Gastrointest Oncol. 2021 Apr 15;13(4):197-215. doi: 10.4251/wjgo.v13.i4.197.

..

Downloads

Published

2024-03-07 — Updated on 2024-03-08

Versions