It is rate that we get medicine to admit that a “primitive” vitamin deficiency can directly cause cancer, but the study below is one such example. Namely, the study found that a protein over-produced in the absence of dietary vitamin K or pharmacological antagonism of vitamin K has direct oncogenic effects and can cause HCC de-novo, even in the absence of a pre-condition such as a hepatitis B infection or exposure to carcinogens. Now, the fact that vitamin K deficiency is wide-spread is well-known to medicine and public health authorities such as the FDA have already mandated that processed foods be fortified with vitamin K. However, another more sinister finding of the study is that vitamin K antagonism, usually by pharmacological agents, can also trigger the cancer process in the liver. One would think that pharmacological antagonism to vitamin K would be something rare and only apply to a very small number of people. To the contrary, it actually concerns a very large segment of the population who take so-called “blood thinners” as prevention therapy for ischemic events (strokes and heart attacks). The most widely used vitamin K antagonist therapy for ischemic events is the drug warfarin, based on the naturally-occurring molecule coumarin. As of today, more than 3 million people in the US take warfarin on a regular basis, and another 10-20 million take it sporadically due to newly discovered blood clots or deep-vein thrombosis. The study below suggests that all those people may be at direct risk of iatrogenic liver cancer. Coincidentally (not!), multiple pharma companies are running late-stage clinical trials with vitamin K (MK-4) as both prevention and treatment of HCC. Once again, it seems Big Pharma is getting ready to sell us both the poison and the remedy.
https://www.xiahepublishing.com/2310-8819/JCTH-2025-00377
https://www.eurekalert.org/news-releases/1113800
“…Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, particularly in regions with high hepatitis B virus prevalence. Early detection is challenging due to the limited sensitivity of conventional biomarkers such as alpha-fetoprotein (AFP). Protein induced by vitamin K absence or antagonist-II (PIVKA-II), an abnormal prothrombin variant, has emerged as a promising serological biomarker with significant diagnostic, prognostic, and therapeutic relevance in HCC. This review synthesizes current knowledge on the molecular basis, clinical utility, and future directions of PIVKA-II in HCC management.”
“…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 impaired γ-glutamyl carboxylase activity. Structurally, PIVKA-II lacks normal coagulation function due to incomplete carboxylation of glutamic acid 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 through the KDR/PLCγ/MAPK axis. A specialized variant, next-generation DCP (NX-DCP), exhibits higher specificity for HCC and correlates with microvascular invasion and tumor burden.”
