Table 1.
Supplementation of vitamin K in cholestatic liver disease.
| Subject | Dose-Duration | Outcome | Ref. | Year |
|---|---|---|---|---|
| Animal Studies | ||||
| Males and females BDL Sprague–Dawley rats | First dose = 50 µg of VK1, subcutaneously at the time of operation, and the same dose once per week thereafter for two years | In four weeks, the mortality rate decreased from approximately 20–25% to 10%. There was no difference in the extent of hepatic damage or any hemodynamic or biochemical parameters between VK-treated and untreated rats. The reduction in mortality rate was possibly due to a reduction in hemorrhagic complications, contributing to excess mortality. | [62] | 1995 |
| Male BDL Sprague–Dawley rats | MF or NMF diet supplemented with VK3 and VD Survival experiment was done until 50 days. |
Supplementary VK in the diet ameliorated massive internal hemorrhage and prolonged the survival period. | [58] | 2005 |
| Male BDL Sprague–Dawley rats | After BDL, one group of rats was treated by intramuscular injection of VK1 once per week at a dose of 8 mg/kg for four weeks. Drinking water containing gentamicin (160 mg/L) was given to all animals. | The levels of biochemical parameters, fibrotic score, collagen content, α-SMA, and CK19 expression were significantly reduced by treatment with VK1. | [47] | 2014 |
| Human Studies | ||||
| 1–6 months infant with cholestasis | Single dose of 10 mg of VK1 or 10 mg of Konakion biweekly for six months, followed by 10 mg of MM solution, a formulation of VK solubilized in glycocholate and lecithin, biweekly either orally or intramuscularly for over three months | Konakion (VK1) MM efficiently and safely corrected VK deficiency | [61] | 1992 |
| Human | Not known | VK was not useful for cirrhosis, but can be supplemented parenterally only during cholestasis | [85] | 1999 |
| Women with PBC | All were administered UDCA (600 mg/day) during hospitalization. Half of the patients were randomly selected to receive 45 mg/day of MK-4 orally for at least two years. | BMD increased after one year of treatment with MK-4, but returned to near the baseline after two years. However, BMD continued to be significantly higher in the treated group than in the control group throughout the two years of treatment. | [68] | 2001 |
| Patients with PBC | 2 mg/day of VK orally for 12 months. All the patients received oral calcium (1 g/day) and VD (20 μg/day) for one month prior to randomization and continued throughout the study. BMD scanning of the spine (L2–L4) and femoral neck was performed at 0 and 12 months. | No significant effect of VK treatment was found. | [86] | 2003 |
| Patients with cholestasis | 7.8–700 μg/kg/day of oral VK The duration of the supplementation is not known. |
VK intake was positively correlated with the severity of cholestasis. No correlation was found with PT, INR, and PIVKA-II levels. | [57] | 2009 |
| Patients with chronic liver failure | Daily intramuscular injection of 10 mg of VK1 followed up for 48 weeks | VK1 reduced the INR levels as well as the risk of death | [69] | 2020 |
BDL, bile duct ligation; VK, vitamin K; MK-4, menaquinone-4; VD, vitamin D; α-SMA, α-smooth muscle actin; CK19, cytokeratin 19; UDCA, ursodeoxycholic acid; BMD, bone mineral density; PT, prothrombin time; INR, international normalized ratio; PIVKA-II, protein induced by vitamin K absence or antagonist-II.