Des-γ-carboxy prothrombin in the diagnosis of primary hepatocellular carcinoma: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

DE Ji ¹ , YANG Li ² ,  WANG Yiping ²

1. Tibetan Hospital of Tibet Autonomous Region, Lhasa, 850000, P.R.China;
2. Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

WANG Yiping, Email: wyplm2012@163.com

Keywords：

Des-γ-carboxy prothrombin; Diagnosis value; Primary hepatocellular carcinoma; Meta-analysis

DOI：

10.7507/1672-2531.201909033

Video：

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Objective To systematically review clinical value of des-γ-carboxy prothrombin (DCP) in the diagnostic of primary hepatocellular carcinoma (PHC).Methods Databases including PubMed, The Cochrane Library, EMbase, Medline (Ovid), CNKI, VIP, WanFang Data and CBM were electronically searched to collect relevant studies on DCP in the diagnosis of PHC from inception to December 31^st, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using Meta-Disc 1.4 software and RevMan 5.3 software.Results A total of 50 studies involving 15 099 cases were included. The results of meta-analysis showed that the pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, pooled diagnostic odds ratio and area under the curve of SROC were 0.69 (95%CI 0.67 to 0.70), 0.89 (95%CI 0.89 to 0.90), 7.35 (95%CI 6.08 to 8.90), 0.31 (95%CI 0.27 to 0.35), 26.63 (95%CI 20.42 to 34.73) and 0.909 9, respectively.Conclusions Serum DCP has higher diagnostic efficacy for PHC, especially with higher specificity of diagnosis. Due to the limited quality and quantity of included studies, the above results should be validated by more studies.

Citation： DE Ji, YANG Li, WANG Yiping. Des-γ-carboxy prothrombin in the diagnosis of primary hepatocellular carcinoma: a systematic review. Chinese Journal of Evidence-Based Medicine, 2020, 20(7): 798-808. doi: 10.7507/1672-2531.201909033 Copy

1.	Gomaa AI, Khan SA, Leen ELS, et al. Diagnosis of hepatocellular carcinoma. World J Gastroenterol, 2009, 15(11): 1301-1314.
2.	Tamura Y, Igarashi M, Suda T, et al. Fucosylated fraction of alpha-fetoprotein as a predictor of prognosis in patients with hepatocellular carcinoma after curative treatment. Dig Dis Sci, 2010, 55(7): 2095-2101.
3.	Inagaki Y, Tang W, Makuuchi M, et al. Clinical and molecular insights into the hepatocellular carcinoma tumour marker des-γ-carboxyprothrombin. Liver Int, 2011, 31(1): 22-35.
4.	Carr BI, Kanke F, Wise M, et al. Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci, 2007, 52(3): 776-782.
5.	Volk ML, Hernandez JC, Su GL, et al. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark, 2007, 3(2): 79-87.
6.	Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3(2): 25-38.
7.	Devillé WL, Buntinx F, Bouter LM, et al. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol, 2002, 2: 9.
8.	Bachtiar I, Kheng V, Wibowo GA, et al. Alpha-1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low hepatocellular carcinoma. BMC Res Notes, 2010, 3: 319.
9.	Beale G, Chattopadhyay D, Gray J, et al. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer, 2008, 8: 200.
10.	Choi JY, Jung SW, Kim HY, et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol, 2013, 19(3): 339-346.
11.	Cui R, He J, Zhang F, et al. Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein. Br J Cancer, 2003, 88(12): 1878-1882.
12.	Durazo FA, Blatt LM, Corey WG, et al. Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol, 2008, 23(10): 1541-1548.
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15.	Huang S, Jiang F, Wang Y, et al. Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients. Tumour Biol, 2017, 39(6): 1010428317705763.
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18.	Marrero JA, Su GL, Wei W, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology, 2003, 37(5): 1114-1121.
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24.	Sassa T, Kumada T, Nakano S, et al. Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. Eur J Gastroenterol Hepatol, 1999, 11(12): 1387-1392.
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1. Gomaa AI, Khan SA, Leen ELS, et al. Diagnosis of hepatocellular carcinoma. World J Gastroenterol, 2009, 15(11): 1301-1314.
2. Tamura Y, Igarashi M, Suda T, et al. Fucosylated fraction of alpha-fetoprotein as a predictor of prognosis in patients with hepatocellular carcinoma after curative treatment. Dig Dis Sci, 2010, 55(7): 2095-2101.
3. Inagaki Y, Tang W, Makuuchi M, et al. Clinical and molecular insights into the hepatocellular carcinoma tumour marker des-γ-carboxyprothrombin. Liver Int, 2011, 31(1): 22-35.
4. Carr BI, Kanke F, Wise M, et al. Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci, 2007, 52(3): 776-782.
5. Volk ML, Hernandez JC, Su GL, et al. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark, 2007, 3(2): 79-87.
6. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol, 2003, 3(2): 25-38.
7. Devillé WL, Buntinx F, Bouter LM, et al. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol, 2002, 2: 9.
8. Bachtiar I, Kheng V, Wibowo GA, et al. Alpha-1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low hepatocellular carcinoma. BMC Res Notes, 2010, 3: 319.
9. Beale G, Chattopadhyay D, Gray J, et al. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer, 2008, 8: 200.
10. Choi JY, Jung SW, Kim HY, et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol, 2013, 19(3): 339-346.
11. Cui R, He J, Zhang F, et al. Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein. Br J Cancer, 2003, 88(12): 1878-1882.
12. Durazo FA, Blatt LM, Corey WG, et al. Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol, 2008, 23(10): 1541-1548.
13. Ertle JM, Heider D, Wichert M, et al. A combination of alpha-fetoprotein and des-gamma-carboxy prothrombin is superior in detection of hepatocellular carcinoma. Digestion, 2013, 87(2): 121-131.
14. Grazi GL, Mazziotti A, Legnani C, et al. The role of tumor markers in the diagnosis of hepatocellular carcinoma, with special reference to the des-gamma-carboxy prothrombin. Liver Transpl Surg, 1995, 1(4): 249-255.
15. Huang S, Jiang F, Wang Y, et al. Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients. Tumour Biol, 2017, 39(6): 1010428317705763.
16. Kuromatsu R, Tanaka M, Shimauchi Y, et al. Usefulness of ED036 kit for measuring serum PIVKA-II levels in small hepatocellular carcinoma. J Gastroenterol, 1997, 32(4): 507-512.
17. Lok AS, Sterling RK, Everhart JE, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology, 2010, 138(2): 493-502.
18. Marrero JA, Su GL, Wei W, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology, 2003, 37(5): 1114-1121.
19. Marrero JA, Feng Z, Wang Y, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology, 2009, 137(1): 110-118.
20. Mittal A, Gupta SP, Sathian B, et al. Des-gamma-carboxyprothrombin for early identification and prognosis of hepatocellular carcinoma: a case control study from western Nepal. Asian Pac J Cancer Prev, 2012, 13(11): 5773-5775.
21. Morota K, Nakagawa M, Sekiya R, et al. A comparative evaluation of Golgi protein-73, fucosylated hemopexin, alpha-fetoprotein, and PIVKA-II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Clin Chem Lab Med, 2011, 49(4): 711-718.
22. Nakamura S, Nouso K, Sakaguchi K, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol, 2006, 101(9): 2038-2043.
23. Okuda H, Nakanishi T, Takatsu K, et al. Measurement of serum levels of des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma by a revised enzyme immunoassay kit with increased sensitivity. Cancer, 1999, 85(4): 812-818.
24. Sassa T, Kumada T, Nakano S, et al. Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. Eur J Gastroenterol Hepatol, 1999, 11(12): 1387-1392.
25. Seo SI, Kim HS, Kim WJ, et al. Diagnostic value of PIVKA-Ⅱ and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol, 2015, 21(13): 3928-3935.
26. Sharma B, Srinivasan R, Chawla YK, et al. Clinical utility of prothrombin induced by vitamin K absence in the detection of hepatocellular carcinoma in Indian population. Hepatol Int, 2010, 4(3): 569-576.
27. Sterling RK, Jeffers L, Gordon F, et al. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol, 2009, 7(1): 104-113.
28. Tang XQ, Li H, Yan LB, et al. Diagnostic value of PIVKA-II in detecting hepatocellular carcinoma. Future Virol, 2017, 12(5): 259-267.
29. Wang CS, Lin CL, Lee HC, et al. Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma. World J Gastroenterol, 2005, 11(39): 6115-6119.
30. Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol, 2009, 44(7): 861-866.
31. Yu R, Xiang X, Tan Z, et al. Efficacy of PIVKA-II in prediction and early detection of hepatocellular carcinoma: a nested case-control study in Chinese patients. Sci Rep, 2016, 6(2): 35050.
32. 卜丽莎, 刘也, 朴松旭. 异常凝血酶原含量的测定及其在肝癌诊断中的临床应用. 白求恩医科大学学报, 2000, 26(5): 482-484.
33. 陈小红, 崔儒涛, 王宝恩, 等. PIVKA 在肝细胞癌诊断中的价值. 临床消化病杂志, 2002, 14(4): 156-159.
34. 费乐学, 高建超. 血清AFP-L3、GPC3、DCP及TSGF四者联合检测对原发性肝癌的早期诊断价值研究. 标记免疫分析与临床, 2018, 25(3): 407-409+420.
35. 付水, 齐娟飞, 朱海燕, 等. DCP、AFP-L3和AFP在原发性肝细胞癌诊断中的价值. 放射免疫学杂志, 2013, 26(1): 75-78.
36. 傅美丽. 血清异常凝血酶原检测在肝癌患者中的应用. 中外医疗, 2015, 34(28): 116-118.
37. 胡晓菲, 於建鹏, 王钢胜. PIVKA-II和AFP在原发性肝癌中的诊断和疗效监测中的临床应用价值. 临床和实验医学杂志, 2017, 16(15): 1473-1476.
38. 邝妙欢, 欧阳文婷, 林建华, 等. 甲胎蛋白异质体3、异常凝血酶原、甲胎蛋白检测肝细胞癌的对照研究. 中华普通外科学文献(电子版), 2010, 4(4): 311-314.
39. 李生, 林英辉, 潘元平, 等. AFP, AFU 和 DCP 联合检测对PHC的诊断意义. 安徽医药, 2013, 17(10): 1720-1722.
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