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      Diagnostic Value of Combined Detection via Protein Induced by Vitamin K Absence or Antagonist II, Alpha-Fetoprotein, and D-Dimer in Hepatitis B Virus-Related Hepatocellular Carcinoma

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          Abstract

          Purpose

          We aimed to explore the clinical diagnostic value of combined detection via protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), and D-dimer (D-D) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

          Materials and Methods

          We analyzed PIVKA-II, AFP, and D-D levels in 291 subjects comprising liver cirrhosis (LC) patients (n = 143) and HCC patients (n = 148). Receiver operating characteristic (ROC) curves were used to analyze and compare the clinical diagnostic value of the three biomarkers for HBV-related HCC alone and in combination.

          Results

          The levels of PIVKA-II, AFP, and D-D were positively correlated with tumor size in HCC patients. The levels of PIVKA-II and AFP in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients were higher than those in LC patients, while the levels of D-D were lower. The area under the curve for combined detection was greater than that for single-index detection in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients.

          Conclusion

          D-D may be a useful biomarker for the diagnosis of HBV-related HCC. The combined detection of PIVKA-II, AFP, and D-D had better diagnostic value for different types of HCC than the detection of individual biomarkers.

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          Most cited references31

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          Hepatocellular carcinoma

          Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.
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            A global view of hepatocellular carcinoma: trends, risk, prevention and management

            Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.
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              Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases

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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                23 June 2022
                2022
                : 15
                : 5763-5773
                Affiliations
                [1 ]Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University , Changsha, 410005, People’s Republic of China
                [2 ]Operating Room, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University , Changsha, 410005, People’s Republic of China
                Author notes
                Correspondence: Hao Yuan, Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University , Changsha, 410005, People’s Republic of China, Tel +8613677366519, Email yuanhao666@hunnu.edu.cn
                Author information
                http://orcid.org/0000-0002-4000-4538
                Article
                362359
                10.2147/IJGM.S362359
                9236167
                35770053
                644c5f0a-a607-40ef-a28c-381bf5b792da
                © 2022 Peng et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 February 2022
                : 15 June 2022
                Page count
                Figures: 4, Tables: 7, References: 31, Pages: 11
                Funding
                Funded by: National Development and Reform Commission Project;
                This work was supported by National Development and Reform Commission Project (No. 2019X000M045).
                Categories
                Original Research

                Medicine
                pivka-ii,alpha-fetoprotein,d-dimer,biomarker,hepatocellular carcinoma,hepatitis b virus
                Medicine
                pivka-ii, alpha-fetoprotein, d-dimer, biomarker, hepatocellular carcinoma, hepatitis b virus

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