Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Period | Country | Study-Type | Patients | No | Cut-Off PIVKA II | Cut-Off AFP |
---|---|---|---|---|---|---|---|
Schotten C 2021 [53] | 2008–2020 | Germany | Retrospective study | 182 patients with HBV, 223 with HCV, 168 with other etiology, HCC—52 HBV, 84 HCV and 60 | 573 | NA | 20 ng/mL |
Choi J 2019 [54] | NA | Korea | Matched case-control | 42 HCC; 168 cirrhosis or chronic B hepatitis | 210 | 20 mAU/mL | 5 ng/mL |
Best 2020 [55] | 2005–2016 | Germany Japan | Multicenter case-control study | 126 patients with HCC; 231 patients without HCC, NASH controls | 357 | NA | NA |
Wu M 2020 [56] | NA | China | Observational study | 176 healthy, CHB, LC; 198 very early HCC + early HCC + advance and HCC | 374 | NA | NA |
Malov SI 2021 [57] | NA | Russia | Case-control study | 110 patients with chronic hepatitis C in the stage of liver cirrhosis 55 without HCC; 55 with HCC | 110 | 20 ng/mL | 20 ng/mL |
Chan 2022 [58] | NA | China Germany Japan Thailand. | Multicenter prospective study | 168 HCC, 208 patients without HCC with an at-risk condition—cirrhosis, non-cirrhotic chronic hepatitis B virus (HBV), non-cirrhotic chronic hepatitis C virus (HCV), NASH | 376 | 28.4 ng/mL | 20 ng/mL |
Chalasani 2021 [59] | NA | ClinicalTrials.gov | International, multicenter, case-control study | 136 HCC, 404 controls at-risk patients with chronic liver disease—HCV, NAFLD, ASH, HBV, other chronic liver disease | 540 | NA | 20 ng/mL |
Basile 2020 [12] | NA | Italy | Case-control study | 20 metabolic, 40 viral newly diagnosed HCC, 20 healthy subjects | 80 | 38 mAU/mL, | 3.5 ng/mL |
Nouso K 2019 [60] | 2001–2016 | Japan | Case-control study | 172 tumor-free diabetes mellitus, 93 consecutive NBNC-HCC patients | 265 | 20 mAU/mL | 3 ng/mL |
Hemken P 2019 [61] | 2003–2016 | SUA | Retrospective case-control study | 119 HCC, 215 nonmalignant liver disease, 34 healthy | 368 | NA | NA |
Unic A 2018 [62] | 2009–2011 | Croatia | Consecutively recruited study | 20 healthy volunteers, 31 patients with alcoholic liver cirrhosis, 32 patients with HCC. | 83 | 108 mAU/mL | NA |
Liu Z 2020 [63] | 2010–2018 | China | Retrospective study | 87 AFP-negative HBV-related HCC, 123 control cases—benign liver disease, chronic HBV infection or liver cirrhosis | 210 | 45 mAU/mL | NA |
Song T 2021 [64] | 2010–2020 | China | Cross-sectional study | 48 chronic HBV infection (CHB), 64 liver cirrhosis (LC), 33 early-stage CHB-HCC, 55 early-stage LC-HCC. | 200 | 44 mAU/mL | 5 ng/mL |
Loglio A 2020 [65] | 2010–2020 | Italy | Cross-sectional, case-control study | 64 with HCC (cases), 148 HCC-free (control) | 212 | 48 mAU/mL | 4.2 ng/mL |
Caviglia 2020 [1] | 2012–2018 | Italy | Cross-sectional study | 149 HCC, 200 cirrhosis of viral etiology | 349 | 73 mAU/mL | 9.7 ng/mL |
Caviglia 2021 [21] | 2012–2020 | Italy | Retrospective case-control study | 191 NAFLD patients cohort, 72 of whom had a diagnosis of HCC, 119 non-HCC patients | 191 | 56 mAU/mL | 4.4 ng/mL |
Chen H 2018 [66] | 2013–2014 | China | Cross-sectional, consecutively recruited study | 202 HCC patients, 226 liver cirrhosis patients, 215 chronic hepatitis B virus-infected 203 healthy | 846 | NA | NA |
Piratvisuth T 2022 [67] | 2014–2016 | China Germany Spain Thailand | Case-control study | 308 HCC, 740 chronic liver disease—cirrhotic liver disease independent of etiology, noncirrhotic NASH, chronic HBV infection, chronic HCV infection | 1048 | NA | NA |
Song T 2020 [68] | 2014–2017 | China | Prospective study | 100 HCC in patients with hepatitis B virus (HBV)—associated liver cirrhosis (LC), 67 LC | 167 | 38 mAU/mL | 10 ng/mL |
Degasperi E 2021 [69] | 2014–2019 | Italy | Retrospective study | 34 HCC, 366 non-HCC patients | 400 | 47 mAU/mL | 17 ng/mL |
Wu J 2018 [70] | 2016–2017 | China | Case-control study | 51 healthy, 37 chronic hepatitis, 43 cirrhotic; 143 HCC | 274 | 40 mAU/mL | 10 ng/mL |
Qi F 2020 [71] | 2016–2018 | China | Prospective study | 120 HCC, 89 chronic liver disease—nonviral, autoimmune, fatty-liver, HBV, HCV | 209 | 33.08 mAU/mL | 11.88 ng/mL |
Li Y 2019 [72] | 2016–2018 | China | Retrospective study | Group 1 non-cancer, Group 2 primary cancer in liver patients—not available the numbers | 1190 | 60.5 mAU/mL | NA |
Guan MC 2022 [73] | 2016–2020 | China | Retrospective observational study | 139 HCC, 345 NAFLD | 484 | 40 mAU/mL | 20 ng/mL |
Si YQ 2020 [74] | 2017–2018 | China | Case-control study | 266 cases with HBV-related HCC, 87 HBV DNA-positive benign liver disease, 80 healthy individuals | 433 | 41.74 mAU/mL | 21.8 ng/mL |
Ji J 2021 [75] | 2017–2018 | China | Cross-sectional, multicenter study | 183 HCC-CHB- and HBV-related, 312 cases were chronic hepatitis and 289 cases were cirrhosis | 784 | 40 mAU/mL | 20 ng/mL |
Wang G 2020 [76] | 2017–2018 | China | Retrospective study | 234 HBV-related HCC, 396 patients with chronic hepatitis B (CHB) | 630 | 87.63 mAU/mL | 499.80 ng/mL |
Bhatti 2020 [6] | 2017–2019 | Pakistan | Retrospective study | Cirrhotic patients, surgical candidates—176 HCC, 68 non-HCC | 244 | 250 mAU/mL | 7.6 ng/mL |
Wang Q 2019 [77] | 2017–2019 | China | Retrospective study | 176 HBV-related HCC, 359 patients with chronic hepatitis B. | 535 | 162.22 mAU/mL | 145.65 ng/mL |
Li T 2019 [78] | 2017–2019 | China | Case-control study. | 169 newly diagnosed early HCC, 242 LC without HCC | 411 | NA | NA |
Feng H 2021 [79] | 2017–2019 | China | Case-control study. | 168 HCC patients,150 benign liver disease, 153 healthy controls | 469 | 35.60 mAU/mL | 17.76 ng/mL |
Nguyen HB 2022 [80] | 2018–2019 | Vietnam | Case-control study. | 170 chronic hepatitis B virus, hepatitis C virus, 170 HCC | 340 | 29.01 mAU/mL | 5.1 ng/mL |
Lee Q 2021 [81] | 2018–2020 | China | Prospective study | 158 primary HCC in chronic hepatitis B, 62—chronic hepatitis B | 220 | 34.92 mAU/mL | 9.10 ng/mL |
Chen J 2020 [82] | 2019 | China | Case-control study | 110 patients HBV-associated HCC, 70 HBV-related LC, 70 CBH, 110 healthy | 360 | 51.00 mAU/mL | 5.65 ng/mL |
Xu F 2021 [83] | 2019 | China | Retrospective study | 308 HCC, 60 HBV-related LC, 60 benign liver disease | 428 | 40 mAU/mL | 25 ng/mL |
Peng F 2022 [84] | 2020–2021 | China | Prospective study | 143 LC, 148 hepatitis B virus (HBV)-related hepatocellular carcinoma | 291 | NA | NA |
Hadi H 2022 [85] | 2021–2022 | Malaysia | Cross-sectional study | HCC—in relationship with 26 HBV, 12 NASH, 2 HCV, 123 nonmalignant high-risk liver cirrhosis | 163 | 36.7 mAU/mL | 14.2 ng/mL |
Study | AUC PIVKA II | AUC AFP | Se PIVKA II % | Sp PIVKA II % | Se AFP % | Sp AFP % |
---|---|---|---|---|---|---|
Schotten C 2021 [53] | 0.920 | 0.890 | - | - | - | - |
Choi J 2019 [54] | 0.710 | 0.770 | 48.00 | 86.00 | 62.00 | 87.00 |
Best 2020 [55] | 0.870 | 0.880 | - | - | - | - |
Wu M 2020 [56] | 0.634 | 0.798 | 29.80 | 97.20 | 77.30 | 71.10 |
Malov SI 2021 [57] | 0.760 | 0.630 | 54.60 | 88.60 | 45.50 | 94.50 |
Chan 2022 [58] | 0.908 | 0.880 | 86.90 | 83.70 | 51.80 | 98.10 |
Chalasani 2021 [59] | - | 0.840 | - | - | 46.00 | 88.00 |
Basile 2020 [12] | 0.790 | 0.900 | - | - | - | - |
Nouso K 2019 [60] | - | 0.885 | - | - | 81.80 | 82.60 |
Hemken P 2019 [61] | 0.870 | 0.880 | 86.00 | 72.00 | 86.00 | 77.00 |
Unic A 2018 [62] | 0.903 | - | 81.25 | 96.77 | - | - |
Liu Z 2020 [63] | 0.731 | - | 50.60 | 94.30 | - | - |
Loglio A 2020 [65] | 0.776 | 0.750 | 64.00 | 91.00 | 56.00 | 94.00 |
Caviglia 2020 [1] | 0.790 | 0.737 | 68.00 | 84.00 | 72.00 | 66.00 |
Caviglia 2021 [21] | 0.853 | 0.763 | 75.00 | 85.70 | 76.40 | 68.90 |
Chen 2018 [66] | 0.820 | 0.720 | 65.20 | 90.00 | 43.70 | 90.00 |
Degasperi E 2021 [69] | 0.780 | 0.630 | 76.00 | 79.00 | 29.00 | 97.00 |
Qi F 2020 [71] | 0.835 | 0.810 | 83.50 | 71.60 | 73.60 | 80.70 |
Guan MC 2022 [73] | 0.869 | 0.763 | 74.80 | 91.00 | 52.50 | 97.40 |
Si YQ 2020 [74] | 0.901 | 0.765 | 81.20 | 88.50 | 51.50 | 89.70 |
Ji J 2021 [75] | 0.932 | - | 84.08 | 90.43 | 61.33 | 91.15 |
Wang G 2020 [76] | 0.925 | 0.745 | 86.80 | 90.20 | 52.10 | 91.40 |
Bhatti 2020 [6] | 0.720 | 0.830 | 72.00 | 60.00 | 77.00 | 77.00 |
Wang Q 2019 [77] | 0.913 | 0.744 | 81.30 | 93.60 | 64.80 | 77.20 |
Li T 2019 [78] | 0.890 | 0.900 | 84.20 | 82.00 | 85.30 | 85.60 |
Feng H 2021 [79] | 0.900 | 0.770 | 83.93 | 91.50 | 64.29 | 90.20 |
Nguyen HB 2022 [80] | 0.925 | 0.910 | 91.00 | 76.00 | 73.00 | 92.00 |
Lee Q 2021 [81] | 0.836 | 0.799 | 68.4 | 98.40 | 57.60 | 93.50 |
Chen 2020 [82] | 0.935 | 0.826 | 85.00 | 93.00 | 84.10 | 70.90 |
Xu F 2021 [83] | 0.900 | 0.790 | 89.00 | 91.70 | 68.80 | 87.60 |
Hadi H 2022 [85] | 0.905 | 0.869 | 90.00 | 82.10 | 75.00 | 93.50 |
Study | No | AUC PIVKA II | AUC AFP | Se PIVKA II % | Sp PIVKA II % | Se AFP % | Sp AFP % |
---|---|---|---|---|---|---|---|
Schotten C 2021 [53] | 70 | 0.830 | 0.860 | - | - | - | - |
Choi J 2019 [54] | 31 | - | 0.800 | - | - | - | - |
Wu M 2020 [56] | 113 | 0.613 | 0.723 | 25.70 | 97.20 | 67.30 | 71.70 |
Chalasani 2021 [59] | 81 | - | 0.780 | - | - | - | - |
Liu Z 2020 [63] | 62 | 0.685 | - | 43.50 | 94.30 | - | - |
Song T 2021 [64] | 88 | 0.747 | 0.794 | 55.70 | 88.40 | 65.90 | 88.40 |
Caviglia 2020 [1] | 115 | 0.766 | 0.708 | 65.00 | 84.00 | 67.00 | 66.00 |
Caviglia 2021 [21] | 47 | 0.810 | 0.704 | - | - | - | - |
Chen 2018 [66] | 94 | 0.730 | 0.620 | 48.30 | 90.00 | 30.60 | 90.00 |
Piratvisuth T 2022 [67] | 125 | 0.790 | 0.834 | 56.00 | - | 53.60 | - |
Song T 2020 [68] | 100 | 0.750 | 0.760 | 60.00 | 84.70 | 51.50 | 92.50 |
Guan MC 2022 [73] | 60 | 0.851 | 0.752 | 75.00 | 89.60 | 46.70 | 97.40 |
Wang G 2020 [76] | 94 | 0.851 | 0.617 | 72.30 | 90.20 | 33.00 | 92.40 |
Wang Q 2019 [77] | 74 | 0.835 | 0.621 | 68.90 | 89.70 | 47.30 | 29.95 |
Li T 2019 [78] | 95 | 0.890 | 0.900 | 84.20 | 82.00 | 85.30 | 85.60 |
Peng F 2022 [84] | 59 | 0.871 | 0.599 | 61.20 | 95.80 | 28.81 | 97.90 |
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Perne, M.G.; Sitar-Tăut, A.-V.; Alexescu, T.G.; Ciumărnean, L.; Milaciu, M.-V.; Coste, S.-C.; Vlad, C.-V.; Cozma, A.; Sitar-Tăut, D.-A.; Orăşan, O.H.; et al. Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Diagnostics 2023, 13, 816. https://doi.org/10.3390/diagnostics13050816
Perne MG, Sitar-Tăut A-V, Alexescu TG, Ciumărnean L, Milaciu M-V, Coste S-C, Vlad C-V, Cozma A, Sitar-Tăut D-A, Orăşan OH, et al. Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Diagnostics. 2023; 13(5):816. https://doi.org/10.3390/diagnostics13050816
Chicago/Turabian StylePerne, Mirela Georgiana, Adela-Viviana Sitar-Tăut, Teodora Gabriela Alexescu, Lorena Ciumărnean, Mircea-Vasile Milaciu, Sorina-Cezara Coste, Calin-Vasile Vlad, Angela Cozma, Dan-Andrei Sitar-Tăut, Olga Hilda Orăşan, and et al. 2023. "Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis" Diagnostics 13, no. 5: 816. https://doi.org/10.3390/diagnostics13050816