vitamin-k-semiquinone-radical and Liver-Cirrhosis--Biliary

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

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.

Topics: Animals; Disease Models, Animal; Hemorrhage; Hemostasis; Ligation; Liver Cirrhosis, Biliary; Male; Rats; Rats, Sprague-Dawley; Survival Rate; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To determine the occurrence of fat-soluble vitamin deficiencies and to identify clinical factors that may predict vitamin deficiency in patients with primary biliary cirrhosis (PBC).. Review of our data from a randomized, placebo-controlled trial that evaluated the efficacy of UDCA in 180 patients with PBC. We use the first available measurements of vitamin levels in each study participant. Vitamin levels for A, D, and E were measured in serum. The prothrombin time (PT) was used as a surrogate marker for vitamin K.. The proportion of patients with fat-soluble vitamin deficiencies in the treatment and placebo groups was similar and the data sets were combined. The proportion with vitamin A, D, E or K deficiency was 33.5%, 13.2%, 1.9%, and 7.8%, respectively. In multivariate analysis, the Mayo risk score, advanced histological stage, and total cholesterol were independently associated with vitamin A deficiency whereas serum albumin levels was independently associated with vitamin D deficiency. No factors were associated with vitamin E or K deficiency in multivariate analysis owing to the few vitamin E and K deficient patients. Factors predictive of vitamin K deficiency by univariate analysis included Mayo risk score, advanced histological stage, HDL, total bilirubin, AST, and albumin. The cut-off value of the Mayo risk score with the highest sensitivity and specificity for vitamin A deficiency was 5.0.. Other than deficiency of vitamin A, deficiency of fat-soluble vitamins occurs uncommonly in patients with PBC. A Mayo risk score > or = 5 helps in selecting patients with PBC for surveillance for vitamin A deficiency.

Topics: Adult; Aged; Humans; Liver Cirrhosis, Biliary; Middle Aged; Regression Analysis; Solubility; Vitamin A; Vitamin D; Vitamin E; Vitamin K

A patient with primary biliary cirrhosis (PBC) developed marked hypoprothrombinemia with decreased concentrations of the vitamin K-dependent coagulation factors VII, IX, and X during treatment with rifampicin. The coagulation abnormalities were easily corrected by administration of vitamin K. Different mechanisms may be involved, such as a decreased production of menaquinones by intestinal bacteria, a warfarin-like effect by inhibition of the vitamin K epoxide reductase, or an increased oxidative degradation of vitamin K as a result of hepatic microsomal enzyme stimulation. Whatever the mechanism involved, the appearance of this complication in a patient with PBC probably points to the importance of a pre-existing poor vitamin K status. Patients with PBC, treated with rifampicin, should have a regular monitoring of their vitamin K status. Adequate vitamin substitution should be administered, if necessary.

Topics: Female; Humans; Hypoprothrombinemias; Liver Cirrhosis, Biliary; Middle Aged; Prothrombin Time; Rifampin; Vitamin K; Vitamin K Deficiency

Topics: Anticholesteremic Agents; Child; Cholestyramine Resin; Dietary Fats; Humans; Liver Cirrhosis, Biliary; Triglycerides; Vitamin A; Vitamin D; Vitamin E; Vitamin K

We measured serum levels of vitamins A, E, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D, as well as levels of abnormal (des-gamma-carboxy) prothrombin, in 52 patients with primary biliary cirrhosis. Decreased serum levels of retinol (vitamin A) and 25-hydroxyvitamin D and elevated levels of abnormal prothrombin were common in these patients and correlated with the histologic stage of the disease and with the clinical severity of disease as judged by elevated serum bilirubin levels and decreased serum albumin levels. The increased levels of abnormal prothrombin were due primarily to vitamin K deficiency but also, in part, to the severity of the liver disease itself. Vitamin E deficiency was rare. Only 1 patient had clinical manifestations of fat-soluble vitamin deficiency, night blindness, and gastrointestinal bleeding related to a marked prolongation of the prothrombin time. Deficiencies of fat-soluble vitamins are most likely to be present in jaundiced patients with long-standing, severe cholestasis. We suggest that fat-soluble vitamin status be determined in all patients with primary biliary cirrhosis by appropriate blood tests and that vitamin supplements be given only to those patients who require them.

Topics: Biomarkers; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Protein Precursors; Prothrombin; Serum Albumin; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Adult; Aged; Antibodies; Bile Ducts; Cholic Acids; Female; Humans; Immunity, Cellular; Kidney Function Tests; Liver; Liver Cirrhosis, Biliary; Lymphocyte Activation; Male; Middle Aged; Mitochondria, Liver; 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: Alcoholism; Anemia; Anemia, Hypochromic; Avitaminosis; Cholestyramine Resin; Common Bile Duct; Diet; Diet Therapy; Diuretics; Folic Acid; Folic Acid Deficiency; Gastrointestinal Hemorrhage; Humans; Hydrochlorothiazide; Ion Exchange Resins; Jaundice; Liver Cirrhosis; Liver Cirrhosis, Biliary; Postoperative Complications; Prothrombin Time; Vitamin B 12; Vitamin B Complex; Vitamin K