What is the role of vitamin K (Vitamin K1, phylloquinone) in acute hepatitis?

Mechanism of Vitamin K in Acute Hepatitis

Primary Mechanism and Hepatic Function

Vitamin K serves as an essential cofactor for hepatic microsomal enzymes that catalyze post-translational carboxylation of glutamic acid residues in inactive precursors of coagulation factors II, VII, IX, and X, converting them into active clotting factors that are secreted into the bloodstream. 1

The mechanism operates through the following pathway:

• Vitamin K enables gamma-carboxylation of specific peptide-bound glutamic acid residues in hepatic precursors of vitamin K-dependent clotting factors 1
• The resulting gamma-carboxy-glutamic acid residues convert inactive precursors into functional coagulation factors 1
• These activated factors are then secreted by liver cells into the circulation 1

Critical Limitation in Acute Hepatitis

In acute hepatitis, vitamin K has minimal to no efficacy in correcting coagulopathy because the primary problem is impaired hepatic synthetic function, not vitamin K deficiency. 2

The key mechanistic distinctions are:

• True vitamin K deficiency results in adequate hepatic synthetic capacity but lack of substrate (vitamin K) for carboxylation, leading to production of undercarboxylated (inactive) clotting factors 3
• Acute hepatitis causes hepatic synthetic dysfunction, where damaged hepatocytes cannot produce adequate amounts of clotting factor precursors regardless of vitamin K availability 2
• Vitamin K can only be effective when patients have experienced prolonged antibiotic therapy, poor nutrition, or severe malabsorption—conditions creating true vitamin K deficiency rather than synthetic dysfunction 2

Biomarkers of Vitamin K Status vs. Hepatic Dysfunction

PIVKA-II (protein induced by vitamin K absence) measurement quantifies undercarboxylated prothrombin species and serves as a sensitive biomarker of hepatic subclinical vitamin K deficiency. 3

However, in acute hepatitis:

• Preprothrombin (PIVKA-II) can appear in peripheral blood even without vitamin K deficiency, indicating liver parenchymal damage 4
• The presence of PIVKA-II in acute viral hepatitis may reflect hepatocellular injury rather than vitamin K deficiency, particularly when pseudocholinesterase levels are subnormal 4
• Fibrinogen levels help distinguish between vitamin K deficiency (normal fibrinogen) and liver synthetic dysfunction (low fibrinogen <100-150 mg/dL in advanced disease) 2

Clinical Efficacy and Timing

When vitamin K is administered intravenously in acute hepatitis, the action is generally detectable within 1-2 hours, with hemorrhage usually controlled within 3-6 hours if vitamin K deficiency is the underlying cause. 1

Important temporal considerations:

• Maximum effect for IV administration occurs at 6-12 hours, while oral supplementation requires approximately 24 hours 3
• Vitamin K takes more than 12 hours to begin correcting hemostatic defects and typically has only minor impact on prothrombin time in patients with hepatic synthetic dysfunction 2
• A normal prothrombin level may be obtained in 12-14 hours only when vitamin K deficiency (not synthetic dysfunction) is the primary problem 1

Evidence Against Routine Use in Liver Disease

Subcutaneous vitamin K does not modify coagulation parameters in liver disease, and routine correction of elevated INR with vitamin K is not supported by evidence in the absence of active bleeding. 2

Research demonstrates:

• Vitamin K administration (10 mg subcutaneously) did not cause significant improvements in Factor VII, protein C, or protein S levels across patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma 5
• No significant changes occurred in prothrombin time, activated partial thromboplastin time, or fibrinogen levels 72 hours after vitamin K administration 5
• Progressive increments in baseline PIVKA-II with decrements in clotting factors across disease severity suggest synthetic dysfunction rather than vitamin K deficiency as the primary mechanism 5

Specific Indications in Acute Hepatitis

Vitamin K should be administered at 5-10 mg intravenously in acute hepatitis only when there is clinical suspicion of concurrent vitamin K deficiency (cholestasis, malabsorption, prolonged antibiotics, or malnutrition). 2, 6

The diagnostic approach includes:

• Administer vitamin K 10 mg IV or subcutaneously and recheck INR after 12-24 hours 2
• Improvement in INR by ≥0.5 within 24-72 hours confirms a vitamin K deficiency component 2
• Lack of response indicates hepatic synthetic dysfunction as the primary mechanism 2

Anti-inflammatory Properties

Vitamin K status has been associated with lower concentrations of inflammatory markers in vivo and may exert an anti-inflammatory role by suppressing NF-κB signal transduction. 3

This mechanism is distinct from its coagulation function:

• The anti-inflammatory effect operates through modulation of inflammatory signaling pathways 3
• This property may be relevant in acute hepatitis where inflammation drives hepatocellular injury, though clinical evidence for therapeutic benefit is limited 3

Safety Considerations

Doses exceeding 10 mg can create a prothrombotic state and prevent re-anticoagulation for days, while IV administration carries a rare risk (3 per 100,000 doses) of anaphylactoid reactions with bronchospasm and cardiac arrest. 3, 2, 6

Administration precautions:

• Administer IV vitamin K by slow injection to minimize anaphylactoid reaction risk 6
• The reaction is non-IgE mediated, possibly due to the solubilizer in the vitamin K solution 6
• Monitor for hypersensitivity during and after administration 6