vitamin-k-semiquinone-radical and Cholestasis

This article provides an update on fat-soluble vitamins (A, D, E, and K) in the healthy pediatric population and in children with chronic disease states that commonly cause deficiencies, specifically cystic fibrosis and cholestatic liver disease. For each fat-soluble vitamin, the biological function, nutrition availability, absorption, deficiency, toxic states, and monitoring parameters are defined.

Topics: Avitaminosis; Child; Cholestasis; Cystic Fibrosis; Humans; Pediatrics; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangiopathy are cholestatic liver diseases of unknown cause. Destruction of small to medium bile ducts (in primary biliary cirrhosis and autoimmune cholangiopathy) and large bile ducts (in primary sclerosing cholangitis) leads to progressive cholestasis, liver failure and end-stage liver disease. A variety of abnormalities in lipid metabolism have been described in primary biliary cirrhosis, and range from alterations in serum lipid levels and lipoprotein subsets to deranged metabolism of cholesterol. Progressive cholestasis and, consequently, decreased small intestinal bile acid concentrations in these cholestatic liver disease can also lead to impaired absorption of fats and fat-soluble vitamins, resulting in steatorrhea and deficiencies in vitamins A, D, E, and K. This article focuses on abnormalities in lipid metabolism in primary biliary cirrhosis and primary sclerosing cholangitis, and on lipid-activated vitamin deficiencies in these disorders.

Topics: Avitaminosis; Cholangitis, Sclerosing; Cholestasis; Chronic Disease; Fatty Liver; Humans; Lipid Metabolism; Liver Cirrhosis, Biliary; Malabsorption Syndromes; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

1. Hepatocyte couplets can be routinely prepared from rat liver to produce a suitable in vitro model for polarized primary cells. 2. Centrifugal elutriation provides a means of producing enriched subpopulations of periportal and perivenous couplets from the same liver, thus providing a means of studying the influence of zonal heterogeneity on hepatobiliary function. 3. The maintenance of structural and secretory polarity demonstrated by hepatocyte couplets provides a convenient in vitro system for mechanistic studies of factors both regulatory and adversely affecting hepatobiliary functions. 4. Couplets are also uniquely appropriate for specific studies of regulation at the biliary pole, on the performance of junctions and on the maintenance and rate of transcytotic movement. 5. The possibility also exists that effects of an in vivo pre-exposure to agents causing hepatobiliary dysfunction can be assessed in couplets ex vivo.

Topics: Animals; Bile Acids and Salts; Bile Canaliculi; Cell Communication; Cell Separation; Cells, Cultured; Cholestasis; Cyclosporine; Hemostatics; Immunosuppressive Agents; In Vitro Techniques; Liver; Rats; Tight Junctions; Vacuoles; Vitamin K

Coagulation disorders in liver disease (cirrhosis or acute hepatic necrosis) may be assessed by the laboratory evaluation of factors V, VII, VIII and IX, and fibrinolysis. Tests of platelet and vascular function do not significantly contribute to this assessment. The response of the factors to vitamin K and to fresh frozen plasma contribute to the assessment of bleeding potential and prognosis.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cholestasis; Disseminated Intravascular Coagulation; Fibrinolysis; Humans; Liver Cirrhosis; Vitamin K

Topics: Bile Ducts, Intrahepatic; Cholestasis; Cholestyramine Resin; Drainage; Ergocalciferols; Humans; Vitamin E; Vitamin K

Topics: Antibodies, Antinuclear; Antibody Formation; Cholangitis; Cholestasis; Cholestyramine Resin; Complement System Proteins; Hepatitis A; Humans; Liver Cirrhosis; Vitamin A; Vitamin K

Topics: Adult; Alkylation; Biological Transport; Celiac Disease; Cholestasis; Dietary Fats; Feces; Humans; Infant; Intestinal Absorption; Intestines; Lipid Metabolism; Malabsorption Syndromes; Oxides; Pancreatitis; Tritium; Vitamin K; Vitamin K 1; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Flow Velocity; Blood Platelet Disorders; Blood Transfusion; Cholestasis; Chronic Disease; Diagnosis, Differential; Factor V; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Liver; Liver Diseases; Platelet Adhesiveness; Prognosis; Prothrombin Time; Vitamin K

Topics: Alkaline Phosphatase; Aspartate Aminotransferases; Bile Acids and Salts; Bile Ducts; Bile Ducts, Intrahepatic; Bilirubin; Cell Division; Chenodeoxycholic Acid; Cholangiography; Cholestasis; Cholic Acids; Coloring Agents; Diagnosis, Differential; Humans; Liver; Liver Function Tests; Mitochondria, Liver; Pruritus; Vitamin K

Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients.. We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an international normalized ratio (INR) for prothrombin time (PT), a surrogate marker for vitamin K deficiency, were measured.. The proportion of patients with FSV A, D, E, and K deficiencies under conventional supplementation was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total bilirubin levels ≥3.0  mg/dL, the proportion of at least 1 FSV deficiency was 100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%, 100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose of OAFSV for 3 months, no adverse events or overdose effects were found. The rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3 months of oral supplementation.. High rates of FSV deficiency were found in pediatric patients with chronic cholestasis under present follow-up. OAFSV supplementation is safe and potentially effective in pediatric patients with cholestasis.

Topics: Administration, Oral; Adolescent; Alagille Syndrome; Avitaminosis; Biliary Atresia; Bilirubin; Child; Child, Preschool; Cholestasis; Cholestasis, Intrahepatic; Dietary Supplements; Female; Humans; Infant; Male; Solubility; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

To evaluate the efficacy of oral menadiol compared to intravenous phytomenadione when correcting coagulopathies associated with cholestasis.. A total of 26 patients with cholestasis and an international normalized ratio (prothrombin time) greater than 1.2, were randomized to receive either 20 mg o.d. for 3 days of oral menadiol (n=12), or 10 mg o.d. of intravenous phytomenadione (n=14) prior to endoscopic retrograde cholangeopancreatography. Liver function tests and international normalized ratio were measured daily for 3 days.. Liver function tests and international normalized ratio were comparable between groups at entry into the study (P > 0.05), but serum albumin was significantly lower in the intravenous phytomenadione group following treatment (P < 0.05). A decrease in international normalized ratio occurred in both groups following administration of vitamin K (P < 0.05). Two patients in the intravenous group required fresh frozen plasma, as failure to normalize international normalized ratio was observed. No adverse drug reactions were observed in either group, and no patient required re-admission for bleeding during a 4-week follow-up period after cholangeopancreatography.. Oral menadiol appears to be an effective alternative to intravenous phytomenadione in the correction of coagulopathies associated with obstructive liver disease. This simplifies the care of patients with deranged clotting times requiring cholangeopancreatography, particularly those to be managed as out-patients.

Topics: Aged; Aged, 80 and over; Blood Coagulation Disorders; Cholestasis; Female; Humans; Male; Middle Aged; Prothrombin Time; Vitamin K; Vitamin K 1

Infants with cholestasis are at risk of fat-soluble vitamin deficiency. The present study amied to review practice relating to the assessment, deficiency and supplementation of fat-soluble vitamins in infants with cholestasis.. In total, 136 infants (87 male) with idiopathic neonatal cholestasis (n = 62), biliary atresia (n = 40) and other aetiology (n = 34) were included. Assessment of serum vitamins (A, D, E) was low (33.3%-52.2%) and deficiency was initially high for vitamin D (60.6%) and vitamin E (70.9%). Supplementation prevalence at initial assessment was high (A, E, K), but dropped significantly at 3 and 6 months for vitamin E (p = 0.003) and vitamin K (p = 0.001), whereas vitamin D supplementation was consistently low throughout (25%-33.3%). Infants with biliary atresia were more likely to have vitamins assessed (3 months), be deficient initially (D, E) and supplemented (E, K) throughout. Supplementation continued in up to 80% of infants despite cholestasis resolving.. Supplementation was generally high and continued in many despite cholestasis resolving. Deficiency of vitamin D and vitamin E was high at initial assessment, although lower at follow-up. Actual prevalence of deficiency of all vitamins is unknown because monitoring was not consistently performed.

Topics: Biliary Atresia; Bilirubin; Cholestasis; Dietary Supplements; Female; Humans; Infant; Infant, Newborn; Male; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Administration, Oral; Animals; Antifibrinolytic Agents; Bile; Biological Availability; Cholestasis; Disease Models, Animal; Drug Compounding; Gastrointestinal Absorption; Male; Micelles; Rats; Rats, Wistar; Vitamin K

Infants who are born in The Netherlands receive oral vitamin K to prevent bleeding due to a vitamin K deficiency. However the incidence of such bleedings are higher compared to other European countries. Therefore, the Dutch Health Council advised in 2017 to change this guideline from oral to intramuscular administration.. A 2 months old girl presented with a fatal intracranial hemorrhage. A day before she developed a hematoma on her foot and orbit. Despite daily oral vitamin K, blood results revealed a severe vitamin K deficiency-related bleeding. Postmortem liver biopsy and genetic studies showed cholestasis as the most likely cause of malabsorption of fat soluble vitamins due to a heterozygous pathogenic variant in the ABCB11 gene, which could possibly be transient.. Our case illustrates the importance of revising the national guideline for vitamin K prophylaxis to intramuscular administration, according to the recommendation of the Dutch Health Council.

Topics: Cholestasis; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Vitamin K; Vitamin K Deficiency Bleeding

Vitamin K is a fat-soluble compound that plays important roles in coagulation. In children with intestinal failure-associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil-based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency.. Ten neonates with IFALD and receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK). Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing.. The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19-78) days. During cholestasis reversal, INR remained relatively unchanged, whereas the mean (95% confidence interval) daily fecal excretion of PK increased from 25.1 (5.0-158.5) ng at the time of FOLE initiation to 158.5 (31.6-1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR revealed little correlation between the 2 measurements (r = -0.10; P = 0.50).. Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status.

Topics: Child; Cholestasis; Fat Emulsions, Intravenous; Humans; Infant, Newborn; International Normalized Ratio; Male; Parenteral Nutrition; Vitamin K

Available evidence suggests that patients with short bowel syndrome (SBS) might be at risk of vitamins A, D, E and B(1) deficiency. However, there is little clinical data describing the vitamin K status. Therefore, in the present study we aimed to assess the body resources of vitamin K in a subset of SBS patients.. The study comprised 33 patients aged 1 month to 16 years. PIVKA-II concentrations were determined in all subjects.. In all studied subjects, coagulation parameters were normal. PIVKA-II levels indicative of vitamin K deficiency was found in 3 (9.1%) SBS patients. One patient had been receiving an additional intravenous vitamin K dose of 5 mg/week. In all SBS patients with cirrhosis and cholestasis, PIVKA-II concentrations were low (<2 ng/ml). However, all patients with severe liver disease were receiving vitamin K several times a month.. Vitamin K deficiency may appear in SBS patients.

Topics: Adolescent; Antifibrinolytic Agents; Biomarkers; Blood Coagulation; Child; Child, Preschool; Cholestasis; Female; Humans; Infant; Liver Cirrhosis; Male; Protein Precursors; Prothrombin; Short Bowel Syndrome; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K deficiency in infants can cause life-threatening haemorrhages. To prevent this, neonates in the Netherlands receive an oral dose of 1 mg vitamin K directly after birth. In addition, because breast milk contains little vitamin K, breast-fed infants receive a daily dose of 25 micrograms the first three months. Of three female infants aged 4 weeks, 5 months and 3 months, respectively, two developed an intracranial haemorrhage, which caused death in one. In two cases there were signs of a bleeding tendency, but no tests were done because the patients appeared healthy otherwise. The underlying resorptive disorders, cholestasis and fat malabsorption, caused few symptoms and were discovered only after a vitamin K deficiency bleeding had occurred. In an infant with a bleeding tendency, one should consider the possibility of vitamin K deficiency, even if adequate prophylaxis has been given.

Topics: Antifibrinolytic Agents; Breast Feeding; Cholestasis; Fatal Outcome; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Lipid Metabolism, Inborn Errors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

We studied, retrospectively, 92 children who were first seen with neonatal cholestasis and who were followed up until liver test results normalized. Among the 92 children, 81 displayed factors responsible for chronic and/or acute perinatal distress. Onset of jaundice was recorded at a mean age of 7 days, and mean duration was 3.5 months. Stools, initially discolored in 39 children, were normally colored at a mean age of 1.7 months. Hepatomegaly present in 90 children resolved at a mean age of 13 months. Liver test results were normal at the age of 1 year in 83 children and normalized at a mean age of 10 months. Liver histologic examination, performed in 70 children, showed moderate portal and lobular fibrosis, multinucleated giant hepatocytes, and hematopoietic foci; findings in follow-up liver biopsy specimens from 15 children were normal or improved. Spontaneously resolving forms of neonatal cholestasis may result from the association of several factors, including immaturity of bile secretion and perinatal disease leading to hepatic hypoxia or ischemia.

Topics: Alanine Transaminase; Biopsy; Cholangiography; Cholestasis; Female; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Liver; Male; Prothrombin Time; Retrospective Studies; Vitamin K

Topics: Blood Coagulation Disorders; Cholestasis; Humans; Preoperative Care; Prospective Studies; Vitamin K

We have measured the plasma PIVKA-II levels in 188 cases of various liver disease with HCC and malignant diseases in other organs by an EIA, using a monoclonal antibody (E-1023 kit, Eisai), and also have measured the plasma vitamin K levels in cases of HCC and cholestasis by an HPLC. Plasma PIVKA-II was detected in many cases of HCC (67%, 35 of 52 cases) and cholestasis (60%, 6 of 10 cases). In contrast, the positivities of PIVKA-II in the other diseases including benign liver diseases were very low. Combination assays of PIVKA-II and vitamin K revealed that PIVKA-II correlates with vitamin K in cholestasis but not in HCC, suggesting that PIVKA-II in HCC does not depend on a systemic deficiency of vitamin K. From these results, it was concluded that PIVKA-II is a reliable marker which can reflect the clinical course of HCC.

Topics: Adult; Aged; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholestasis; Embolization, Therapeutic; Female; Humans; Immunoenzyme Techniques; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Prothrombin; Vitamin K

A case of malabsorption of vitamin K, leading to a vitamin K-dependent clotting factor deficiency that developed during the eighth gestational month, is reported. Evaluation of the coagulopathy at term showed the cause to be an obstructive hepatobiliary disorder. Given the pathophysiologic relationship between the coagulation cascade and the hepatic and biliary systems, routine measurement of the prothrombin and partial thromboplastin times is advised for all patients with evidence of hepatobiliary dysfunction.

Topics: Adult; Blood Coagulation Disorders; Cholestasis; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin K; Vitamin K Deficiency

To elucidate the etiology of hemostatic abnormalities in cases of obstructive jaundice, we occluded the bile duct of rats for one week and found that the moderately jaundiced rats exhibited a marked reduction in the value of Hepaplastin test and Thrombotest with minimum histological changes in liver. All other coagulation and fibrinolysis profiles were within normal limits. These findings exclude the occurrence of a hypercoagulable state or hypofibrinolytic state in the jaundiced rats due to bile duct occlusion. Similar results were obtained in rats with tube choledochostomy. The abnormalities were almost completely prevented by the daily parenteral administration of vitamin K. These observations suggest that malabsorption of vitamin K may be the sole etiologic factor producing hemostatic defects in case of uncomplicated obstructive jaundice.

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Cholestasis; Fibrinolysis; Male; Rats; Rats, Inbred Strains; Vitamin K

A female patient is described who developed skin and subcutaneous fat necrosis on two occasions after intake of acenocoumarol. Several months later identical skin changes occurred during an episode of cholestasis associated with a prolongation of the prothrombin time to an extent comparable with therapeutic anticoagulation; intake of oral anticoagulants could be excluded. This association gives new insights in the pathogenetic mechanisms responsible for the so-called coumarin necrosis and indicates that it may be not due to drug toxicity or allergy.

Topics: Acenocoumarol; Adipose Tissue; Adult; Blood Coagulation Factors; Cholestasis; Drug Therapy, Combination; Female; Heparin; Humans; Necrosis; Recurrence; Skin Diseases; Thrombophlebitis; Vitamin K

Topics: Animals; Bilirubin; Cholestasis; Dogs; Liver; Liver Diseases; Liver Function Tests; Monoamine Oxidase; Vitamin K

A simple and rapid in vitro test was devised to detect the presence of the prothrombin precursor molecule circulating in the plasma of 55 out of 56 patients receiving oral vitamin K antagonists and in 4 out of 5 patients with obstructive jaundice, using either Dispholidus typus or Echis carinatus venoms. The absence of the molecule from the plasma of jaundiced patients was suggestive of hepatocellular rather than obstructive jaundice. The test is based on the clotting of aluminium hydroxide gel adsorbed plasma by the venoms. It is more sensitive and easier to perform than measuring antigenic prothrombin levels.

Topics: Adsorption; Cholestasis; Cholestasis, Intrahepatic; Diagnosis, Differential; Humans; Jaundice; Prothrombin; Prothrombin Time; Snake Venoms; Vitamin K

Topics: Adult; Cholestasis; Cholestyramine Resin; Female; Humans; Hypoprothrombinemias; Pregnancy; Pregnancy Complications; Vitamin K

The reduction of prothrombin level below 5% in a patient with intrahepatic cholestasis of pregnancy is reported. The necessity of controlling the Quick level or better factors II, VII, IX and X is discussed. A well-timed Vitamin K therapy in all cases with impaired secretion of bile during pregnancy is recommended.

Topics: Blood Coagulation Disorders; Cholestasis; Female; Humans; Pregnancy; Pregnancy Complications, Hematologic; Vitamin K

Topics: Adult; Anemia, Macrocytic; Animals; Child; Cholestasis; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Malabsorption Syndromes; Male; Protein-Energy Malnutrition; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency

Topics: Adult; Biopsy; Calcium; Cholestasis; Chronic Disease; Diagnosis, Differential; Female; Hepatitis; Humans; Liver; Liver Cirrhosis, Biliary; Middle Aged; Prognosis; Vitamin A; Vitamin D; Vitamin K

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Factors; Cholestasis; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Heparin; Hepatitis; Humans; Liver Circulation; Vitamin K

Topics: Alkaline Phosphatase; Bilirubin; Cholestasis; Cholesterol; Cholestyramine Resin; Female; Humans; Liver Diseases; Pregnancy; Pregnancy Complications; Pruritus; Recurrence; Transaminases; Vitamin K

Topics: Antibodies; Asparaginase; Blood Coagulation; Cholestasis; Factor IX; Hemophilia B; Humans; Liver Cirrhosis; Neutralization Tests; Vitamin K

Topics: Celiac Disease; Cholestasis; Humans; Intestinal Absorption; Intestine, Small; Pancreatitis; Tritium; Vitamin K

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cholestasis; Factor IX; Factor VII; Factor X; Factor XII; Humans; Preoperative Care; Thrombelastography; Time Factors; Vitamin K

Topics: Adult; Blood Chemical Analysis; Cholestasis; Cholesterol; Cholestyramine Resin; Female; Humans; Liver Diseases; Liver Function Tests; Pregnancy; Pregnancy Complications; Progesterone; Pruritus; Pruritus Ani; Uterine Hemorrhage; Vitamin K

Topics: Adult; Age Factors; Alkaline Phosphatase; Body Height; Child; Child, Preschool; Cholestasis; Consanguinity; Edema; Fats; Feces; Female; Hemorrhage; Heterozygote; Humans; Hyperbilirubinemia; Hyperlipidemias; Infant; Infant, Newborn; Liver; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Pedigree; Pruritus; Tooth Discoloration; Transaminases; Vitamin K

Topics: Animals; Antifibrinolytic Agents; Biliary Tract; Cholestasis; Heparin Antagonists; Humans; Male; Rabbits; Vitamin K; Vitamin K Deficiency