Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, notably in regions wiht high hepatitis B virus prevalence. Early detection is challenging due to the limited sensitivity of conventional biomarkers such as alpha-fetoprotein (AFP). Vitamin K absence protein-induced protein or protein II (PIVKA-II), an abnormal variant of prothrombin, has emerged as a promising serological biomarker with meaningful diagnostic, prognostic, adn therapeutic relevance in HCC. This review synthesizes current knowledge on the molecular basis,clinical utility,and future directions of PIVKA-II in HCC management.
Introduction
Table of Contents
HCC is the most common form of primary liver cancer, frequently enough diagnosed at an advanced stage due to its asymptomatic onset. The inadequacy of AFP, particularly in AFP-negative HCC (AFP-NHCC), highlights the need for more reliable biomarkers. PIVKA-II, first identified in 1984, has garnered attention for its close association with tumor biology and superior diagnostic performance in certain clinical settings.
Biological significance and characteristics of PIVKA-II
PIVKA-II, also known as des-γ-carboxy prothrombin (DCP), is generated under conditions of vitamin K deficiency or antagonism. In HCC, its production is linked to hypoxia, reduced vitamin K levels, and altered γ-glutamyl carboxylase activity. Structurally, PIVKA-II lacks normal coagulation function due to incomplete carboxylation of glutamate residues in its Gla domain. Beyond being a metabolic byproduct,PIVKA-II actively promotes HCC progression by activating oncogenic pathways such as c-Met/JAK1/STAT3 and Ras/Raf/MEK/ERK,and by stimulating angiogenesis via the KDR/PLCγ/MAPK axis.A specialized variant, next-generation DCP (NX-DCP), exhibits greater specificity.
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Cardiac Hydrographic imaging (CHI) is an emerging technique gaining recognition for its potential to improve the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). Recent research emphasizes its translational value through integration into multiparametric models and clinical guidelines,though standardization and personalized implementation remain key areas for future growth.
Cardiac Hydrographic Imaging (CHI)
Cardiac Hydrographic Imaging (CHI) is a novel, non-invasive imaging modality used to assess cardiac function, particularly focusing on diastolic dysfunction, a hallmark of HFpEF. it measures the velocity and direction of blood flow within the heart chambers, providing insights into cardiac mechanics beyond conventional echocardiography or cardiac MRI.
CHI utilizes advanced Doppler techniques and computational fluid dynamics to create detailed visualizations of blood flow patterns. This allows clinicians to identify subtle abnormalities in ventricular filling and relaxation that may be missed by conventional imaging methods. the technique is particularly valuable in HFpEF, where standard measures of ejection fraction frequently enough appear normal despite significant functional impairment.
For example, a study published in Circulation in 2022 demonstrated that CHI parameters correlated with exercise capacity and pulmonary artery pressure in patients with HFpEF, suggesting its potential to predict disease severity and guide treatment decisions.Source
Heart Failure with Preserved Ejection Fraction (hfpef)
Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex clinical syndrome characterized by symptoms of heart failure despite a normal left ventricular ejection fraction (typically ≥50%). It affects a growing population, particularly older adults and women, and is associated with significant morbidity and mortality.
HFpEF is often caused by a combination of factors, including hypertension, obesity, diabetes, and aging. These conditions lead to changes in the heart muscle and vasculature that impair diastolic function - the heart’s ability to relax and fill with blood properly. Diagnosis can be challenging, as traditional imaging methods may not fully capture the subtle abnormalities in cardiac mechanics.
According to the American Heart Association, HFpEF accounts for approximately 50% of all heart failure cases. Source
Role of CHI in Multiparametric Models
CHI is increasingly being integrated into multiparametric models alongside other imaging modalities, biomarkers, and clinical data to improve the diagnosis and risk stratification of HFpEF. These models aim to provide a more comprehensive assessment of cardiac function and identify patients who would benefit most from targeted therapies.
By combining CHI parameters with measures of left ventricular stiffness, pulmonary artery pressure, and natriuretic peptides, clinicians can gain a more nuanced understanding of the underlying pathophysiology of HFpEF. this can lead to more accurate diagnoses and personalized treatment plans.
A 2023 review article in the Journal of the American College of Cardiology: Heart Failure highlighted the potential of multiparametric models incorporating CHI to predict adverse outcomes in HFpEF patients. Source
Future Directions and Standardization
Despite its promise, the widespread adoption of CHI is currently limited by a lack of standardization in testing protocols and data analysis. Future research should focus on establishing standardized methods to ensure reproducibility and comparability of results across different centers.
Further inquiry into the underlying mechanical mechanisms of CHI signals is also needed to improve our understanding of its relationship to cardiac function and disease progression. Ultimately, the goal is to develop personalized approaches to CHI interpretation and implementation, tailoring treatment strategies to the individual needs of each patient.
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