vitamin-k-semiquinone-radical and Hepatitis

Antithyroid drugs (ATDs) have been widely and effectively used for the treatment of pediatric and adult thyrotoxicosis for more than a half century. Since the very beginning of ATD use, reports of hepatic dysfunction related to propylthiouracil (PTU) therapy have been published. We describe a case of a 12-year-old girl, who, after 4 weeks of therapy for Graves disease (GD) with PTU (300 mg/day at 100 mg given three times a day), developed fatigue, fever, diarrhea, nausea, and vomiting. The initial diagnosis was "viral gastrointestinal infection". Few days after the initiation of her symptoms, the patient developed jaundice, hepatic tenderness, and dark urine. She was admitted to the hospital where, after an extensive investigation, it was found that serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were elevated (2312 and 1435 IU/L, respectively), alkaline phosphatase (ALP) was 171 IU/L and total bilirubin was 12.7 mg/dL, whereas direct bilirubin was 7.6 mg/dL and prothrombin time was 23.2 s (normal ratio, < 14.5 s). Serology for hepatitis A and B was negative. The diagnosis of PTU-induced hepatitis was established. PTU was discontinued, and a treatment with prednisone (50 mg/day) and vitamin K was initiated. Four weeks after admission, her hepatic tests returned to normal. We searched the English literature and we present details of all cases with PTU-related hepatic toxicity in children and adolescents published so far. Also, we provide information regarding the mechanisms and treatment of this appalling clinical entity. Finally, after recent recommendations from American Thyroid Association (ATA) and European Thyroid Association (ETA), PTU should be administered only in the first trimester of pregnancy and in cases of drug allergy to methimazole.

Topics: Antithyroid Agents; Child; Female; Graves Disease; Hepatitis; Humans; Liver Function Tests; Propylthiouracil; Review Literature as Topic; Vitamin K

Topics: Bilirubin; Cholestyramine Resin; Diagnosis, Differential; Eclampsia; Female; Fetus; Hepatitis; Humans; Hyperemesis Gravidarum; Jaundice; Jaundice, Chronic Idiopathic; Liver Diseases; Pregnancy; Pregnancy Complications; Vitamin K

Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.

Topics: Brain; Cholestasis, Intrahepatic; Fatal Outcome; Female; Giant Cells; Hepatitis; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Plasma; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency Bleeding; Vitamins

Topics: Cerebral Hemorrhage; Fatal Outcome; Female; Hepatitis; Humans; Infant, Newborn; Vitamin K

We measured menaquinone-4 (MK-4) and MK-4 epoxide concentrations in plasma and liver tissue after intravenous injection of 200 micrograms/kg MK-4 in 42 patients who underwent hepatectomy. They were classified into normal (N; n = 10), chronic hepatitis (CH; n = 12), and liver cirrhosis (LC; n = 20) groups, on the basis of the diagnosis given by the pathologist after examining resected liver specimens. The plasma MK-4 epoxide concentration reached maximum level (Cmax) 60 min after MK-4 injection. The Cmax in groups LC and CH were 85.9 and 126.3 nmol/l, respectively, which is significantly reduced compared with that of group N (184.4 nmol/l) (p less than 0.01 and p less than 0.05, respectively). The MK-4 concentrations in liver tissues of 24 patients 60 min after MK-4 injection were 2.77 in group N, 3.79 in group CH, and 3.83 nmol/g in group LC, and the MK-4 epoxide concentrations were 4.01, 3.09, and 2.62 nmol/g in the respective groups. Consequently, the ratio of MK-4 epoxide to total MK-4 (MK-4 + MK-4 epoxide) in groups CH and LC was significantly lower than in group N (p less than 0.01). It is concluded that the Cmax of MK-4 epoxide after MK-4 injection may serve as an indicator of liver function and that the low ratio of MK-4 epoxide to total MK-4 in the liver shows impairment in vitamin K metabolism.

Topics: Carcinoma, Hepatocellular; Chronic Disease; Female; Hepatectomy; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Regression Analysis; Vitamin K; Vitamin K 2

By means of staphylocoagulase, plasma des-gamma-carboxy prothrombin (DCP) was measured in 255 subjects. Of these, 59 were healthy controls, 100 had primary hepatocellular carcinoma (PHC), 33 had cirrhosis of the liver, 16 had hepatitis, 11 had metastatic carcinoma of the liver (MCL), and 36 subjects had previously been treated with anti-vitamin K drugs. The mean plasma DCP level in the healthy subjects was 3.02 VGH U/l. Of PHC patients 80% had DCP levels greater than 6 VGH U/l, which we regarded as probably abnormal. None of the patients with benign liver diseases (cirrhosis of liver or hepatitis) had DCP greater than 10 VGH U/l. Of the patients with MCL 54.54% had DCP greater than 6 VGH U/l. In our study DCP was found to be as sensitive a tumor marker as alpha-fetoprotein (AFP) in the diagnosis of PHC and was better in distinguishing PHC from benign liver disease. Of PHC patients 92% had at least one of the two tumor markers. Simultaneous determination of DCP and AFP should be applied in mass survey programs for detecting PHC, especially in countries with a high prevalence of hepatitis B virus infection.

Topics: alpha-Fetoproteins; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Protein Precursors; Prothrombin; Vitamin K

Plasma levels of prothrombin immunoreactive protein (factor II antigen) (II-Ag) and coagulant activity (II-CA) were determined in eight patients with acute hepatitis and in 29 patients with chronic liver disease (cirrhosis). The II-CA was reduced in 23 (62%), II-Ag in 17 (46%), and both were reduced in 13 (36%) of the cases. A disproportionate reduction was noted in 21 (57%); ie, there was more II-Ag found in comparison to the corresponding level of II-Ca. Ninety-six percent (23) of 24 patients with moderate to severe hepatocellular disease showed reduced II-CA levels; 63% (15) showed reduced II-Ag levels, with a disproportionate reduction in II-CA in 67% (16). These data suggest that reduced synthesis as well as impaired carboxylation of prothrombin precursor protein are factors contributing to the coagulopathy in patients with moderate to severe liver disease and that measurement of circulating levels of II-Ag may provide an excellent indication of hepatic synthetic capacity.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Female; Hepatitis; Humans; Infant; Liver; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prothrombin; Vitamin K

Topics: Acute Disease; Aged; Castor Oil; Drug Eruptions; Female; Hepatitis; Humans; Infusions, Parenteral; Solutions; Vitamin K

Relationships between Normotest, prothrombin time, albumin, gamma-globulin, GPT, and the hepatic fractional clearance of 198Au-colloids as a measure of effective hepatic blood flow were studied by correlation analysis, in 50 patients with liver diseases, including chronic hepatitis or cirrhosis. Simple correlation coefficients were highly significant between Normotest, prothrombin time, albumin, and the hepatic fractional clearance; however, not between GPT or gamma-globulin and the other parameters. Further correlation analysis revealed a highly significant partial correlation coefficient between Normotest and albumin and the hepatic clearance; however, not between Normotest and albumin. As effective hepatic blood flow is considered to be proportional to the liver parenchymal volume, the above results indicate that vitamin-K-dependent clotting factors, as well as albumin, reflect the liver cell mass.

Topics: Alanine Transaminase; Blood Coagulation Factors; Chronic Disease; gamma-Globulins; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Prothrombin Time; Serum Albumin; Vitamin K

The decreased capacity of the liver to synthesize proteins is the main cause of decreased blood levels of clotting factors II, V, VII, IX, X and of antithrombin III in patients with liver disease. Therefore, determination of the activity or concentration of these coagulation proteins is a useful test of liver function and guide to prognosis, provided that other mechanisms which may influence the blood level are carefully considered. Clotting factor assays have an only limited value for the differential diagnosis in liver disease.

Topics: Acute Disease; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Tests; Carcinoma, Hepatocellular; Chronic Disease; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Factor XIII; Fibrinogen; Hepatitis; Humans; Jaundice, Chronic Idiopathic; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Liver Neoplasms; Neoplasm Metastasis; Prothrombin; Vitamin K

Alcoholic hepatitis is the precursor of cirrhosis. Susceptibility is independent of amount and duration of ethanol intake or of diet. Centrilobular hyalin, the key morphologic abnormality, sensitizes lymphocytes to secrete factors which may account (in part) for necrosis, liver cell destruction, increased collagen synthesis and development of cirrhosis. Diagnosis may be facilitated by detection of alcoholic hyalin antigen (AHAg) and antibody (AHAb) in serum of patients with alcoholic hepatitis. Treatment requires abstinence. Steroids have not reduced mortality rates. Measures to improve immunologic reactivity may be helpful. Persons unable to abstain should be enrolled in a surveillance group.

Topics: Alcoholism; Anemia; Animals; Diet; Ethanol; Hepatitis; Humans; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; Pyridoxine; Rabbits; Vitamin B 12 Deficiency; Vitamin K

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: Adrenal Cortex Hormones; Azathioprine; Chronic Disease; Diet Therapy; Hepatitis; Humans; Lipotropic Agents; Prednisolone; Vitamin B 12; Vitamin K

Topics: Azathioprine; Cholecalciferol; Chronic Disease; Deferoxamine; Glucocorticoids; Hepatitis; Humans; Liver Cirrhosis; Physical Therapy Modalities; Vitamin A; Vitamin K

Topics: Biopsy, Needle; Blood Coagulation Disorders; Hemorrhagic Disorders; Hepatitis; Humans; Hypoprothrombinemias; Infant; Infusions, Parenteral; Iron; Liver Function Tests; Malabsorption Syndromes; Male; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Adipose Tissue; Adolescent; Biopsy; Brain Diseases; Fatty Liver; Female; Hepatitis; Humans; Kidney Diseases; Liver; Virus Diseases; Vitamin K

Topics: Adipose Tissue; Adolescent; Ammonia; Anti-Bacterial Agents; Anticonvulsants; Aspartate Aminotransferases; Blood Glucose; Brain Diseases; Child; Child, Preschool; Consciousness; Electroencephalography; Fatty Liver; Female; Glucocorticoids; Glucose; Hepatitis; Humans; Insulin; Intracranial Pressure; Kidney Diseases; Male; Prognosis; Seizures; Vitamin K

Topics: Adipose Tissue; Blood Coagulation Disorders; Brain Diseases; Fatty Liver; Female; Hepatitis; Humans; Infant; Kidney Diseases; Virus Diseases; Vitamin K

Topics: Adipose Tissue; Blood Coagulation Disorders; Brain Diseases; Child, Preschool; Fatty Liver; Glucose; Hepatitis; Humans; Insulin; Kidney Diseases; Male; Mannitol; Peritoneal Dialysis; Remission, Spontaneous; Vitamin K

Topics: Adult; Aged; Animals; Ascorbic Acid; Diagnosis, Differential; Female; Haptoglobins; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Male; Methionine; Middle Aged; Rabbits; Rats; Vitamin K

Topics: Blood Coagulation Disorders; Blood Transfusion; Chemical and Drug Induced Liver Injury; Hemorrhage; Hepatitis; Hepatitis A; Humans; Jaundice; Liver; Liver Diseases; Prothrombin Time; Surgical Procedures, Operative; Transplantation; Vitamin K

Topics: Chemical and Drug Induced Liver Injury; Cholesterol; Chromatography; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Geriatrics; Hepatitis; Hypervitaminosis A; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Oleic Acid; Palmitic Acid; Phospholipids; Toxicology; Vitamin K

Topics: Ascorbic Acid; Drug Therapy; Folic Acid; Hepatitis; Hepatitis A; Humans; Niacinamide; Vitamin B 12; Vitamin B Complex; Vitamin K; Vitamins

Topics: Bilirubin; Blood Chemical Analysis; Blood Coagulation Tests; Blood Protein Electrophoresis; Cholangitis; Hepatitis; Hepatitis A; Humans; Liver Cirrhosis; Liver Function Tests; Prothrombin Time; Serum Albumin; Urine; Vitamin K

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antipyretics; Brucellosis; Chemical and Drug Induced Liver Injury; Diet; Diet Therapy; gamma-Globulins; Hepatitis; Hepatitis A; Hepatitis Viruses; Humans; Hypnotics and Sedatives; Infant; Liver Function Tests; Pregnancy; Prognosis; Steroids; Syphilis; Therapeutics; Vitamin K; Vitamins; Weil Disease

Topics: Adrenocorticotropic Hormone; Anti-Bacterial Agents; Diet; Diet Therapy; Hepatitis; Hepatitis A; Humans; Jaundice; Oxytetracycline; Pathology; Prednisone; Prognosis; Tetracycline; Therapeutics; Vitamin K; Vitamins

Topics: Adolescent; Arginine; Dialysis; Enema; Glucose; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Hydrocortisone; Liver Diseases; Mortality; Neomycin; Pathology; Renal Dialysis; Vitamin K

Topics: Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Blood; Blood Coagulation Factors; Child; D-Alanine Transaminase; Epidemiology; Hepatitis; Hepatitis A; Humans; Liver Function Tests; Vitamin K; Vitamin K Deficiency

Topics: Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Diagnosis; Diet; Diet Therapy; Female; gamma-Globulins; Hepatitis; Hepatitis A; Hepatitis B virus; Hyperemesis Gravidarum; Liver Function Tests; Lupus Erythematosus, Systemic; Methyltestosterone; Norethindrone; Pneumonia; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pyelonephritis; Thioguanine; Toxicology; Vitamin K

Topics: Aspartate Aminotransferases; Australia; Clinical Enzyme Tests; gamma-Globulins; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Humans; Steroids; Vitamin K

Topics: Child; Hepatitis; Hepatitis A; Humans; Infant; Thioctic Acid; Vitamin K; Vitamins

Topics: Blood Coagulation; Blood Coagulation Tests; Fetus; Hematologic Tests; Hemostatics; Hepatitis; Humans; Prothrombin; Vitamin K

Topics: Antifibrinolytic Agents; Hepatitis; Hepatitis A; Humans; Jaundice; Jaundice, Obstructive; Vitamin K

Topics: Antifibrinolytic Agents; Heparin Antagonists; Hepatitis; Humans; Jaundice; Vitamin K

Topics: Antifibrinolytic Agents; Hepatitis; Humans; Vitamin K

Topics: Antifibrinolytic Agents; Estrogens; Hepatitis; Humans; Vitamin K