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

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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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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.
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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. 卜麗莎, 劉也, 樸松旭. 異常凝血酶原含量的測定及其在肝癌診斷中的臨床應用. 白求恩醫科大學學報, 2000, 26(5): 482-484.
33. 陳小紅, 崔儒濤, 王寶恩, 等. PIVKA 在肝細胞癌診斷中的價值. 臨床消化病雜志, 2002, 14(4): 156-159.
34. 費樂學, 高建超. 血清AFP-L3、GPC3、DCP及TSGF四者聯合檢測對原發性肝癌的早期診斷價值研究. 標記免疫分析與臨床, 2018, 25(3): 407-409+420.
35. 付水, 齊娟飛, 朱海燕, 等. DCP、AFP-L3和AFP在原發性肝細胞癌診斷中的價值. 放射免疫學雜志, 2013, 26(1): 75-78.
36. 傅美麗. 血清異常凝血酶原檢測在肝癌患者中的應用. 中外醫療, 2015, 34(28): 116-118.
37. 胡曉菲, 於建鵬, 王鋼勝. PIVKA-II和AFP在原發性肝癌中的診斷和療效監測中的臨床應用價值. 臨床和實驗醫學雜志, 2017, 16(15): 1473-1476.
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