vitamin-k-semiquinone-radical and Liver-Cirrhosis

Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC).. This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC.. A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3.. Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08).. DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Liver Cirrhosis; Prospective Studies; Stroke; Thromboembolism; Vitamin K

Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials.. We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients.. A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020.. Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001).. Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Liver Cirrhosis; Retrospective Studies; Stroke; Vitamin K

Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis.. We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death.. From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I. For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Humans; Indenes; Liver Cirrhosis; Observational Studies as Topic; Portal Vein; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis; Vitamin K

Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients are increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review, we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Disease Progression; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Liver Cirrhosis; Morpholines; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Physicians are occasionally faced with difficult situations in the management of vitamin K antagonists (VKA) due to the lack of sound data available in controlled studies on certain conditions. In this review we would like to address some special but frequent conditions that can be encountered in daily clinical practice. These include the use of VKA in hemodialysis, thromboembolism in patients with liver cirrhosis and the thromboembolic risk in patients who bleed in the course of treatment with VKA. Moreover, two other conditions were examined: what the best way of expressing prothrombin time would be in patients with liver disease and how to behave when a patient treated with VKA shows a subtherapeutic INR. These topics were discussed by a panel of experts during a workshop recently held in Milan by the Italian Federation of Centres for the Diagnosis of Thrombosis and the Surveillance of Antithrombotic Therapies (FCSA). The main aim of the workshop was to provide helpful and practical advice to physicians in the daily management of VKA.

Topics: Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Italy; Liver Cirrhosis; Liver Diseases; Renal Dialysis; Risk Assessment; Thrombosis; Vitamin K; Vitamins

Cirrhotic patients can develop thrombotic complications, which in this group of patients occur with a greater frequency than in the general population. Portal vein thrombosis (PVT) is the most common thrombotic phenomenon, although deep venous thrombosis and pulmonary embolism can also occur. Risk factors for thrombosis include inherited and acquired deficiency of factors involved in anticoagulation mechanisms, venous stasis of the portal vein owing to architectural derangement of the liver and possibly local factors related to the endothelium. Clinical manifestations of PVT range from asymptomatic disease to a life-threatening complication, and although it is no longer considered an absolute contraindication for liver transplant, its presence may require challenging surgical techniques, which entail greater morbidity. Anticoagulation therapy is henceforth an important strategy to treat cirrhotic patients with PVT, although experience in this group of patients is limited. Vitamin K antagonists and low-molecular-weight heparin have been used successfully, achieving recanalization of the thrombosed vessel in patients with cirrhosis; however, the precise drug regimen management and monitoring has not be fully explored in this group of patients.

Topics: Anticoagulants; Contraindications; Heparin; Humans; Incidence; Liver Cirrhosis; Liver Transplantation; Prevalence; Risk Factors; Venous Thrombosis; Vitamin K

Hepatic fibrosis is a common response to virtually all forms of chronic liver injury independent of the etiologic agent. Despite the relatively large population of patients suffering from hepatic fibrosis and cirrhosis, no efficient and well-tolerated drugs are available for the treatment of this disorder. The lack of efficient treatment options is at least partly because the underlying cellular mechanisms leading to hepatic fibrosis are only partly understood. It is thus of pivotal importance to better understand the cellular processes contributing to the progression of hepatic fibrosis. Interestingly in this perspective, a common feature of fibrotic disease of various organs is the activation of the coagulation cascade and hepatic fibrosis is also accompanied by a local hypercoagulable state. Activated blood coagulation factors directly target liver cells by activating protease-activated receptors (PAR) thereby inducing a plethora of cellular responses like (among others) proliferation, migration and extracellular matrix production. Coagulation factor driven PAR activation thus establishes a potential link between activation of the coagulation cascade and the progression of fibrosis. The current review focuses on blood coagulation factor Xa and summarizes the variety of cellular functions induced by factor Xa-driven PAR-2 activation and the subsequent consequences for tissue repair and hepatic fibrosis.

Topics: Animals; Blood Coagulation; Disease Models, Animal; Factor Xa; Humans; Liver; Liver Cirrhosis; Molecular Structure; Receptor, PAR-2; Signal Transduction; Vitamin K

Antiplatelet agents and anticoagulants are effective in the prevention and treatment of a variety of thrombotic disorders. Several clinical settings require more intense antithrombotic regimens. These can be provided by combining (i) two antiplatelet drugs, (ii) antiplatelet monotherapy with an anticoagulant, or (iii) anticoagulation with dual antiplatelet treatment (triple therapy). A major side effect of all antithrombotic regimens, however, is the induction of a bleeding diathesis. This is especially true in patients with preexisting haemostatic defects of any kind that may remain compensated, unless platelet function and/or coagulation are not inhibited pharmacologically. To address the dilemma of the "double-edged sword" between thrombosis and bleeding, several strategies are currently under study, including (i) identification of high-risk patients, (ii) stratification of patient subgroups, (iii) individualized decision making, and (iv) administration of "tailor-made" risk-adapted regimens. Nonetheless, prevention and protection from bleeding in patients using antithrombotic agents remain an enduring challenge. For high-risk patients on antiplatelet agents with urgent need of surgery, an algorithm is discussed that allows short-term interruption of oral antithrombotic therapy and i.v. administration of a GPIIb-IIIa receptor antagonist for bridging without increasing perioperative bleeding. When individual patients, using antiplatelet or anticoagulant agents, experience serious or even life-threatening haemorrhages, haemotherapy with platelet units or prothrombin complex concentrates remains an integral part of the clinical management.

Topics: Anticoagulants; Clinical Trials as Topic; Drug Therapy, Combination; Hemorrhage; Hemostasis; Humans; Liver Cirrhosis; Platelet Aggregation Inhibitors; Risk Factors; Thrombolytic Therapy; Vitamin K

Chronic cholestasis is associated with a variety of symptoms and dysfunction of most organs. Among them, jaundice and pruritus are the first to be recognized, usually prompting the patients to see a physician. Besides the skin, however, cholestasis also affects, inter alia, the metabolism of plasma lipids and fat-soluble vitamins, as well as bone and liver. In the following article the pathogenesis and therapy of metabolic disturbances and organ dysfunctions occurring frequently in patients with chronic cholestasis are discussed.

Topics: Bone Diseases, Metabolic; Cholestasis, Extrahepatic; Humans; Hyperlipidemias; Liver Cirrhosis; Malabsorption Syndromes; Pruritus; Vitamin D; 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

Hemostatic changes in liver cirrhosis regularly have complex causes. In addition to a quantitative deficiency of hemostatic factors, also qualitative changes in coagulation factors, disturbances in coagulation factor metabolism and possible iatrogenic disturbances in plasmatic and thrombocytic hemostatic mechanism are to be considered. To diagnose a deficit of hemostatic factors is no problem, but to answer the question which of the numerous pathogenetic factors dominates in an individual case at this moment is very difficult and often impossible.

Topics: Antithrombin III; Aprotinin; Blood Coagulation Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Erythrocyte Transfusion; Factor XIII; Fibrinogen; Heparin; Humans; Liver Cirrhosis; Platelet Transfusion; Prothrombin; 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; Anti-Bacterial Agents; Fluorouracil; Hemangioma; Hepatic Artery; Humans; Ligation; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Male; Necrosis; Neoplasm Metastasis; Serum Albumin; Vitamin K

Topics: Anti-Bacterial Agents; Blood Transfusion; Cryotherapy; Drainage; Esophageal and Gastric Varices; Esophageal Perforation; Gastrointestinal Hemorrhage; Hemostasis; Hepatic Encephalopathy; Humans; Hypertension, Portal; Intubation, Gastrointestinal; Liver Cirrhosis; Myocardial Infarction; Peptic Ulcer; Pneumonia, Aspiration; Portacaval Shunt, Surgical; Sclerosing Solutions; Therapeutic Irrigation; Ulcer; Vasopressins; Vitamin K

The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.. Retrospective cohort study of patients with cirrhosis prescribed therapeutic anticoagulation over a 3-year period for thrombosis or prevention of stroke in patients with atrial fibrillation. The primary outcomes of interest were bleeding events and recurrent thrombosis or stroke.. During the study period, 27 patients with cirrhosis were prescribed a DOAC and 18 were prescribed VKA or low molecular weight heparin (LMWH). Both groups had similar total bleeding events (8 DOAC vs 10 other, P=.12). There were significantly less major bleeding episodes in the DOAC group (1 [4%] vs 5 [28%], P=.03). Recurrent thrombosis occurred in one patient receiving a DOAC (4%) and one patient (6%) receiving other anticoagulation (P=1.0).. Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Stroke; Thrombosis; Vitamin K

Vitamin K is frequently administered in cirrhotic patients to correct their coagulopathy, but evidence for such practice is lacking. We aimed to assess whether vitamin K administration increases the levels of the vitamin K-dependent factor VII (FVII), protein C, and protein S in patients with different stages of liver dysfunction. Eighty-nine patients were recruited into four groups: group 1 [hepatitis B virus (HBV) inactive carriers, n = 23]; group 2 [chronic HBV and hepatitis C virus (HCV) hepatitis, n = 21]; group 3 (cirrhosis, n = 24); group 4 (hepatocellular carcinoma, n = 21); and a healthy control group (n = 39). A single dose of 10 mg of vitamin K1 was administered subcutaneously to all patients. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, FVII, protein C, total and free protein S, and proteins induced by vitamin K absence (PIVKA)-II (des-gamma-carboxy prothrombin) were measured at baseline and 72 h after vitamin K administration. There was progressive increment in baseline PIVKA-II, and decrements in fibrinogen, FVII, protein C, and protein S across study groups (P < 0.0001). Compared to baseline, vitamin K administration did not affect the measured parameters, whereas TT showed no reduction in any of the groups. Protein C levels declined in group 2, whereas FVII, total and free protein S did not increase in any group, for all parameters. Vitamin K therapy does not cause significant improvements in the majority of coagulation parameters and hence does not seem to be routinely indicated in patients with liver disease.

Topics: Adult; Aged; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Carcinoma, Hepatocellular; Factor VII; Female; Fibrinogen; Hemorrhagic Disorders; Hepatitis B, Chronic; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Protein C; Protein Precursors; Protein S; Prothrombin; Treatment Outcome; Vitamin K; Young Adult

We report here the final analysis of a multicentre randomized, single-blind trial of propranolol for prophylaxis of first bleeding in cirrhosis. One hundred and seventy-four consecutive patients with large esophageal varices were randomly assigned to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (vitamin K: 89 patients). Three were lost to follow-up and 26 had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 3). The cumulative value over 42 months of patients free of bleeding was 74% (95% confidence interval = 85%-63%) in the propranolol and 59% (95% CI = 79%-43%) in the control group and the corresponding survival figures were 51% (95% CI = 63%-39%) and 59% (95% CI = 75%-43%): neither of the differences was significant. A retrospective analysis according to the presence of ascites at randomization showed that in the subset without ascites the proportion of patients free of bleeding was significantly higher in the propranolol group than in the control group (83% vs. 61%; 95% CI = 97%-69% and 78%-44%, respectively; P = 0.028); this difference was even more evident in the ascites-free period (94% vs. 58%; 95% CI = 100%-86% and 76%-40%, respectively; P = 0.002). No differences were found in patients with ascites at randomization. Survival was not significantly affected by treatment in any subgroup, although it was shorter in the ascitic patients given propranolol than in controls (33% vs. 49%; 95% CI = 51%-15% and 71%-27%, respectively; P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Ascites; Clinical Trials as Topic; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Prognosis; Propranolol; Random Allocation; Retrospective Studies; Risk Factors; Vitamin K

The preliminary analysis of a multicentre, randomised, single-blind trial of propranolol for prophylaxis of first bleeding in cirrhosis is reported. 174 consecutively-chosen patients with large oesophageal varices were randomly assigned to either propranolol, in doses which reduced the resting heart rate by 25% (85 patients), or to vitamin K (89 patients). 25 patients had to be withdrawn from treatment with propranolol because of poor tolerance. The 30-month cumulative proportion of patients free of bleeding was 74% in the propranolol group and 63% in the vitamin K group; corresponding survival figures were 59% and 74%, respectively. These differences were not statistically significant. A retrospective analysis, according to the presence of ascites at randomisation showed that a significantly higher proportion of patients without ascites in the propranolol group were free of bleeding compared with those in the control group (87% vs 64%; p = 0.023). No significant differences were found in patients with ascites at randomisation. Length of survival was not significantly affected by treatment in any subgroup, although it was shorter in ascitic patients given propranolol than in controls (33% vs 63%; p = 0.07). If confirmed on a longer follow-up, these results suggest that propranolol could prevent primary variceal haemorrhage in patients with well-compensated cirrhosis.

Topics: Aged; Female; Gastrointestinal Hemorrhage; Hepatitis B Surface Antigens; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Propranolol; Randomized Controlled Trials as Topic; Survival Analysis; Vitamin K

Effects of subcutaneous calcium-heparin and vitamin K administration were studied in 30 cirrhotic patients showing low values of prothrombin time, antithrombin III, fibrinogen, platelet count, plasminogen, alpha 2-antiplasmin, raised levels of fibrin(ogen) degradation products and prolonged activated partial thromboplastin time. A group of 10 patients was first treated with K vitamin for 15 d; after vitamin K therapy interruption, a treatment with 5000 IU (8000 IU in 1 patient) every 12 h of subcutaneous calcium-heparin was started. In another group of 20 patients a treatment with 5000 IU (8000 IU in 2 patients) every 12 h of subcutaneous calcium-heparin was started immediately. The heparin administration in both groups had been performed for at least 2 weeks. No significant changes of blood coagulation picture were observed after vitamin K administration, while calcium-heparin treatment showed an increase in prothrombin time, fibrinogen, platelet count, plasminogen, alpha 2-antiplasmin, a decrease in fibrin(ogen) degradation products and a shortened activated partial thromboplastin time. There was no significant change in antithrombin III values.

Topics: Blood Coagulation Factors; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Fibrinolysis; Heparin; Humans; Liver Cirrhosis; Male; Mononuclear Phagocyte System; Vitamin K

Topics: Clinical Trials as Topic; Diet Therapy; Diuretics; Glucose; Humans; Liver Cirrhosis; Liver Function Tests; Middle Aged; Placebos; Vitamin K

Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing.. This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies.. This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study.. There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed.. In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.

Topics: Adult; Anticoagulants; Blood Coagulation; Case-Control Studies; Humans; International Normalized Ratio; Liver Cirrhosis; Vitamin K; Vitamin K 1; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Humans; Liver Cirrhosis; Neuroprotection; Vitamin K

HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.. In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.. The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of -0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.. Our comprehensive analysis of large sample cohorts validates the GALAD score's utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.

Topics: alpha-Fetoproteins; Biomarkers; Carcinoma, Hepatocellular; Europe; Humans; Latin America; Liver Cirrhosis; Liver Neoplasms; Vitamin K

Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown.. To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis.. We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P < 0.0001). After 52 (3-66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2-12 868) ng/mL and PIVKA-II 80 (22-1813) mAU/mL. EOT-PIVKA-II (HR 3.05, P < 0.0001) and AFP (HR 2.77, P = 0.001) independently predicted HCC together with diabetes (HR 6.12, P < 0.001) and GGT (HR 1.01, P = 0.03). The 4-year cumulative probability of HCC was 24% vs 2% in patients with EOT-PIVKA-II > or ≤41 mAU/mL (P < 0.0001), and 26% vs 9% for EOT-AFP > or ≤15 ng/mL (P = 0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P < 0.0001).. In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.

Topics: Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antiviral Agents; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin; ROC Curve; Vitamin K

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

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.

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

The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates.. This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events.. The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008).. In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Retrospective Studies; Thrombosis; Venous Thrombosis; Vitamin K

To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).. Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients.. Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P <.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P <.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P <.0001).. We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.

Topics: alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Growth Differentiation Factor 15; Hepatitis B; Hepatitis B virus; Humans; Liver Cirrhosis; Liver Neoplasms; Protein Precursors; Prothrombin; ROC Curve; Vitamin K; Vitamins

Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK.. In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group.. There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC.. These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered.

Topics: 4-Hydroxycoumarins; Blood Coagulation Factors; Blood Transfusion; Female; Humans; Indenes; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Retrospective Studies; Vitamin K

Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases.

Topics: Acute Kidney Injury; Administration, Intravenous; Antifibrinolytic Agents; Antithrombins; Dabigatran; Humans; Kidney Tubules; Liver Cirrhosis; Male; Middle Aged; Necrosis; Severity of Illness Index; Treatment Outcome; Vitamin K

Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis.. We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls.. The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times.. In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Humans; Incidence; Italy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Survival Analysis; Thrombosis; Treatment Outcome; Vitamin K

Patients with cirrhosis develop decompensation events during the natural history of the disease that encompass ascites, variceal bleeding, hepatic encephalopathy and jaundice. Coagulation failure, defined using the international normalised ratio, even though not a decompensation event, is important in patients with stratifying cirrhosis into those who require liver transplantation for long-term survival. Isolated coagulation failure in cirrhosis is rare and usually occurs with use of anticoagulants in the setting of vascular diseases. We reported the case of a patient with compensated cirrhosis in whom, isolated severe coagulation failure was found to be due to excessive use of fenugreek milk porridge as part of traditional healing. The coagulation failure was promptly reversed with avoidance of fenugreek and supplementation with vitamin K.

Topics: Antifibrinolytic Agents; Blood Coagulation; Disseminated Intravascular Coagulation; Humans; India; International Normalized Ratio; Liver Cirrhosis; Male; Medicine, Traditional; Middle Aged; Patient Education as Topic; Treatment Outcome; Trigonella; Vitamin K

To investigate the incidence of bleeding events in atrial fibrillation (AF) patients treated with vitamin K (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) screened for the presence of liver fibrosis (LF).. Previous studies provided conflicting results on bleeding risk in AF patients with liver disease on VKAs, and no data on NOACs in this setting are available.. Post-hoc analysis of a prospective, observational multicentre study including 2330 AF outpatients treated with VKAs (n = 1297) or NOACs (n = 1033). Liver damage was quantified by the FIB-4 score (>3.25), a validated marker of LF. The primary endpoint was the incidence of any bleeding, according to ISTH classification.. A high FIB-4 was present in 129 (5.5%) patients: 77 (5.9%) on VKA and 52 (5.0%) on NOACs (p = 0.344). During follow-up, 357 (15.3%) patients experienced a bleeding: 261 (80 major and 180 minor) with VKAs (7.2%/year), and 96 (40 major and 56 minor) with NOACs (6.4%/year). In VKA-treated patients, but not in those on NOACs, FIB-4 >3.25 was associated with higher major bleeding (14.3% vs. 5.6%, log-rank test p < 0.001). Multivariable Cox regression model showed that FIB-4 was associated with major bleeding only in VKA-treated patients (HR: 3.075, 95% CI 1.626-5.818, p = 0.001). On multivariable analysis, FIB-4 was not significantly associated with CVEs neither in VKA or NOAC-treated patients.. We found a significant association between LF and major bleedings in AF patients treated with VKA, which was not evident in patients on NOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Incidence; Liver Cirrhosis; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Vitamin K

Portal vein thrombosis (PVT) is a frequent and serious complication in patients with liver cirrhosis (LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease (compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex end-points such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Severity of Illness Index; Venous Thrombosis; Vitamin K

Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome.. Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium.. Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment.. A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Splanchnic Circulation; Venous Thrombosis; Vitamin K; Young Adult

In recent years there have been advances in the management of non-variceal upper gastrointestinal bleeding that have helped reduce rebleeding and mortality. This document positioning of the Catalan Society of Digestologia is an update of evidence-based recommendations on management of gastrointestinal bleeding peptic ulcer.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Anticoagulants; Biomarkers; Combined Modality Therapy; Comorbidity; Contraindications, Drug; Crystalloid Solutions; Disease Management; Endoscopy, Gastrointestinal; Erythrocyte Transfusion; Erythromycin; Helicobacter Infections; Helicobacter pylori; Hemostatic Techniques; Humans; Hypotension; Intubation, Gastrointestinal; Isotonic Solutions; Liver Cirrhosis; Peptic Ulcer Hemorrhage; Physical Examination; Recurrence; Risk Factors; Vitamin K

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

Topics: Adolescent; Biomarkers; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Humans; Linear Models; Liver Cirrhosis; Male; Osteocalcin; Poland; Prospective Studies; Protein Precursors; Prothrombin; Risk Factors; Vitamin K; Vitamin K Deficiency; Young Adult

The goal of this study was to evaluate the effectiveness of intravenous (IV) vitamin K in cirrhosis.. This was a retrospective study of cirrhotic patients, not on anticoagulation, with administration of IV vitamin K and a baseline INR > 1.5. The primary outcome was the effectiveness of therapy defined by a 30% decrease in INR or a reduction in INR to an absolute value of ≤1.5.. A total of 96 patients were included in the cohort. There was an average decrease in INR of 0.31; however, 60 patients (62.3%) failed to achieve at least a 10% decrease. Sixteen patients (16.7%) met the primary effectiveness endpoint.. The use of IV vitamin K to correct coagulopathy of cirrhosis may not be beneficial.

Topics: Administration, Intravenous; Adult; Antifibrinolytic Agents; Blood Coagulation Disorders; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K

The efficacy of vitamin K in lowering an elevated INR in the setting of cirrhosis is not well established.. The purpose of this investigation is to determine the effect of vitamin K administration on the INR and bleeding eventsamong hospitalized patients with cirrhosis.. This is a retrospective investigation of patients hospitalized at an academic institution from 2010 to 2012. Adults with an ICD9 code supporting cirrhosis were segregated into matched cohorts based on provision of vitamin K. Multivariable logistic regression of factors associated with INR decrease and bleeding events was completed.. The final matched cohort (n = 276) contained 130 patients who received vitamin K and 146 who did not receive this therapy. ICU care (adjusted odds ratio [AOR] = 2.91; 95% CI = 1.54-5.49; P = 0.01), receipt of a blood product (AOR = 2.40; 95%CI = 1.35-4.24; P = 0.03), and baseline INR > 1.6 (AOR = 1.72; 95% CI = 1.00-2.95; P = 0.05), but not vitamin K administration (AOR = 1.17; 95% CI = 0.66-2.08; P = 0.59), were associated with INR decrease. Bleeding events occurred more frequently among patients with a history of esophageal varices (AOR = 6.35; 95% CI = 1.21-33.4; P = 0.03), but vitamin K administration did not have an impact on these events (AOR = 4.90; 95% CI = 0.56-43.0; P = 0.15).. Administration of vitamin K did not affect INR changes or bleeding events in this cohort of hospitalized patients with cirrhosis.

Topics: Adult; Aged; Antifibrinolytic Agents; Female; Hemorrhage; Humans; International Normalized Ratio; Liver Cirrhosis; Male; Middle Aged; Retrospective Studies; Vitamin K

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Venous Thrombosis; Vitamin K

Information on coagulation for cirrhotics on anticoagulants is scanty. We investigated plasma from 23 cirrhotics treated with low-molecular-weight-heparin (LMWH) followed by vitamin K antagonists (VKA).. On days 1-4 patients received full-dose LMWH. On day-5 VKA was started and LMWH was terminated when INR therapeutic-interval was reached. Blood was collected at peak and trough during LMWH, LMWH+VKA and VKA. Non-cirrhotics on VKA were included as controls.. Anti-factor Xa increased from baseline-to-peak during LMWH. During LMWH+VKA was high and reverted to zero during VKA. INR was slightly high at baseline, trough or peak during LMWH and increased to 2.2 during LMWH+VKA or VKA. Mean VKA weekly-doses for cirrhotics and controls were 28.5mg and 28.6mg. Protein C decreased upon VKA, but not to the expected extent. Endogenous-thrombin-potential (ETP) decreased from baseline (1436nMmin) to trough (1258nMmin) and peak (700nMmin) during LMWH and was further reduced during LMWH+VKA (395nMmin).. Target-INR for cirrhotics can be reached by VKA dosages similar to those for non-cirrhotics. ETP reduction parallels the effect of LMWH and/or VKA. Whether these parameters represent the antithrombotic action elicited by these drugs remains to be determined by clinical-trials and laboratory-measurements. ETP, being a global-test reflecting both pro- and anti-coagulants targeted by antithrombotic drugs, seems the candidate for these trials.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Italy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Ultrasonography, Doppler; Venous Thrombosis; Vitamin K

Bleeding is a major concern in treatment of atrial fibrillation (AF) with vitamin K antagonist (VKA). This concern is more emphasized in patients with high bleeding risk such as liver cirrhosis (LC).. We retrospectively analyzed incidence of stroke and major bleeding in 321 AF patients with LC, including early [Child-Pugh (CP)-A, n=215] and advanced [CP-B or C, n=106] LC according to VKA prescription. The CHA2DS2-VASc, HAS-BLED and MELD scores were higher in patients with VKA. CP score was positively correlated with HAS-BLED score (rho: 0.602). The incidence of major bleeding was higher in advanced LC than in early LC (14.5%/year vs. 4.9%/year, p<0.001). VKA reduced the risk of ischemic stroke in AF patients with LC, whereas it significantly increased the major bleeding risk. There was no difference in survival free from significant clinical events (SCEs) between the patients with or without VKA (p=0.91). On subgroup analysis, VKA was beneficial in early LC patients, as it decreased stroke without increasing major bleeding risk. However, in advanced LC patients, VKA significantly increased the risk of major bleeding, especially variceal origin, that overwhelms stroke reduction. As a result, VKA treatment reduced the risk of SCEs in early LC patients, whereas it increased the risk of SCEs in advanced LC.. VKA treatment might be beneficial to reduce significant clinical events in the early LC but not in the advanced LC group. However to confirm this hypothesis, a prospective randomized study is needed.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Liver Cirrhosis; Male; Middle Aged; Prospective Studies; Republic of Korea; Risk Assessment; Vitamin K

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifibrinolytic Agents; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Humans; Liver Cirrhosis; Middle Aged; Octreotide; Plasma; Proton Pump Inhibitors; Vitamin K

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.

Topics: Bile Ducts, Extrahepatic; Biliary Atresia; Cholestasis, Extrahepatic; Encephalocele; Female; Fibrosis; Forensic Pathology; Hematoma, Subdural; Humans; Infant; Liver Cirrhosis; Vitamin K; Vitamin K Deficiency; Vitamins

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

The MELD defines a score used to prioritize patients awaiting liver transplantation and includes results for bilirubin, creatinine and PT expressed as INR. It is assumed that the MELD for individual patients is the same regardless of the laboratory method used for testing, thus ensuring parity of organ allocation. Previous studies showed that the INR calibrated for patients on vitamin K antagonists (INR(vka)) does not normalize results across thromboplastins, whereas an alternative calibration called INR(liver) does. However, implementation of INR(liver) calibration for thromboplastins is difficult in practice. This study aimed to assess whether easy-to-run whole-blood coagulation monitors (widely used for patients on VKA) can be calibrated to measure efficiently the INR(liver) and minimize the interlaboratory variability.. PT values for 61 cirrhotic patients were measured on native-blood with 2 monitors calibrated in terms of INR(vka). PTs for these subjects were also measured with a WHO-standard for thromboplastin. Paired-PTs with the monitors and the standard were subsequently used to calibrate the monitors in terms of INR(liver). INR(vka) and INR(liver) were then compared to assess for statistical significance.. The mean INR(vka) obtained with the monitors and the standard were significantly different (p<0.001). Conversely, the corresponding INR(liver) were not.. The INR(liver) calibration as previously described for thromboplastins works also for the easy-to-run whole-blood coagulation monitors. Once the monitors are calibrated by the manufacturer in terms of INR(liver) they could be used as near-patient-testing devices directly by the personnel of liver units making the determination of the INR for patients awaiting liver transplantation much easier and standardized.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; International Normalized Ratio; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Point-of-Care Systems; Prognosis; Vitamin K; Young Adult

Topics: Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Topics: Dietary Supplements; Eating; Humans; Liver Cirrhosis; Osteoporosis; Vegetables; Vitamin K

The reasons for the decreased functional activity of prothrombin in liver diseases are still speculative. When a highly purified preparation of prothrombin from a patient with liver cirrhosis is available, the cause of prothrombin abnormalities may be researched on a molecular basis. In this study, prothrombin (6.7 mg) was purified from the ascites fluid (1130 mL) of a patient with liver cirrhosis by barium citrate adsorption, ammonium sulfate elution, DEAE Sephacel and Heparin Sepharose CL-6B column chromatography steps. The molecular weight of this prothrombin was the same as that of normal prothrombin purified from a normal plasma pool. The specific activities were found to be 3.36 U/mg in the one stage clotting assay and 28.9 U/mg in the staphylocoagulase/chromogenic substrate assay, while the normal prothrombin specific activities were 3.92 U/mg and 30.1 U/mg respectively. When N-terminal amino acid sequence analysis was carried out, it was seen that the first 20 residues were identical to the normal human prothrombin excepting the Gla at position #14.

Topics: 1-Carboxyglutamic Acid; Amino Acid Sequence; Ascitic Fluid; Glutamic Acid; Hemorrhagic Disorders; Humans; Liver Cirrhosis; Molecular Weight; Protein Processing, Post-Translational; Prothrombin; Prothrombin Time; Vitamin K

The purpose of this study is to determine serum des-gamma-carboxy prothrombin (DCP) levels in benign liver diseases by a new sensitive method, and to demonstrate the elevation of serum DCP in alcoholic liver disease (ALD) without hepatocellular carcinoma (HCC). Median values of serum DCP were 16.2 mAU/ml (range: 3.2 to 1570 mAU/ml) in ALD and 16.7 mAU/ml (1.2 to 75.4 mAU/ml) in viral liver disease (VLD). Using the cut-off value of 40 mAU/ml as a tumor marker for HCC, 21% (11/52) was positive in ALD and 2% (1/57) was positive in VLD (p = 0.0014, Fisher's exact probability test), and 27% (9/33) was positive in alcoholic liver cirrhosis and 3% (1/39) was positive in viral liver cirrhosis (p = 0.0042, Fisher's exact probability test). The positive rate of DCP was significantly (p < 0.001, Spearman's rank correlation test) correlated with the severity of liver disease in ALD. Serum vitamin K level was not decreased in cases with ALD. In a demonstrable case, serum DCP was decreased after abstinence and was increased again after the beginning of ethanol intake, suggesting the involvement of ethanol to the elevation of serum DCP in ALD. In conclusion, serum DCP was significantly elevated in ALD, compared with VLD, although the mechanism of the elevation of DCP was not clarified. Ethanol intake may act, in part, on the increase of serum DCP in ALD.

Topics: Aged; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Ethanol; Female; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin; Reference Values; Vitamin K

Topics: Administration, Oral; Diet; Humans; Injections, Intramuscular; Liver Cirrhosis; Liver Failure; Vitamin K

Topics: Chromatography, High Pressure Liquid; Hepatitis, Chronic; Humans; Indicators and Reagents; Liver; Liver Cirrhosis; Reference Values; Vitamin K; Vitamin K 1

To evaluate the role of bilharzial hepatic fibrosis--whether pure or combined with chronic hepatitis B virus infection--on the functional activity of vitamin K dependent coagulation proteins.. Coagulation screening using prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) was carried out on 31 patients with endemic Egyptian hepatosplenomegaly and on 14 healthy controls. The functional activities of factors II, VII, IX and X and protein C were measured. Patients were classified as pure hepatosplenic schistosomiasis (n = 17) and schistosomiasis with concomitant chronic hepatitis B virus infection (n = 14).. Prolongation of the PT and PTT were noticed in bilharzial patients compared with the controls. The increase in the TT remained within the upper range of normal. Factors II, VII, IX and X and protein C functional activities were significantly reduced in all groups studied.. The decreased activity of vitamin K dependent coagulation factors might be partially offset by the reduced activity of circulating protein C which tends to establish a haemostatic balance at a lower level in endemic Egyptian hepatosplenomegaly. No significant difference could be shown between the pure and mixed cases. Schistosomal coagulopathy is therefore not necessarily aggravated by chronic hepatitis B virus infection.

Topics: Adolescent; Adult; Blood Coagulation Factors; Blood Coagulation Tests; Child; Egypt; Hepatitis B; Hepatomegaly; Humans; Liver Cirrhosis; Male; Middle Aged; Schistosomiasis; Splenomegaly; Vitamin K

Topics: Drug Eruptions; Female; Humans; Injections, Subcutaneous; Liver Cirrhosis; Liver Transplantation; Middle Aged; Skin; 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

Des-gamma-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-II and also abbreviated PIVKA-II, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.

Topics: Adenoma, Bile Duct; alpha-Fetoproteins; Antibodies, Monoclonal; Biomarkers; Carcinoma, Hepatocellular; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Neoplasm Proteins; Neoplasms; Protein Precursors; Prothrombin; Vitamin K

This paper presents a study of treatment involving vitamin K1 (VK1) accompanied by bile acids for hemorrhagic diathesis that was applied 42 times in 35 patients with decompensated liver cirrhosis. The hepaplastin test (HPT) value showed no change during the administration of VK1 alone. The HPT value elevated significantly, however, after the administration of VK1 with bile acid, especially when using ursodeoxycholic acid (UDCA). The HPT value in patients treated with VK1 in addition to UDCA before treatment with 53.2% +/- 10.2% (mean +/- SD) and after that for 2.1 +/- 1.1 months (mean +/- SD) with 74.7 +/- 16.8% showed a significant difference (p less than 0.001). On the other hand, no significant difference was noted between the HPT value of 57.2 +/- 13.6% before and that of 62.9 +/- 13.9% after the treatment in patients treated using VK1 in conjunction with chenodeoxycholic acid (CDCA). These results indicate that the therapy incorporating VK1 and bile acid, especially UDCA, is useful for reducing the hemorrhagic tendency in patients with decompensated liver cirrhosis who show no improvement using VK1 alone.

Topics: Chenodeoxycholic Acid; Deoxycholic Acid; Drug Therapy, Combination; Female; Hemorrhagic Disorders; Humans; Liver Cirrhosis; Male; Ursodeoxycholic Acid; Vitamin K

A patient underwent end-to-side jejunoileostomy for morbid obesity, and 3 years later an end-to-end jejunoileostomy with ileotransversostomy was performed. Nine years later she presented with night blindness, severe diarrhea and mild jaundice and was found to have malabsorption with vitamin A and K deficiencies as well as asymptomatic liver cirrhosis. Her shunt was removed, and a gastric partition was performed. The night blindness and abnormal prothrombin time were corrected by the administration of vitamins A and K. This case demonstrates that complications may appear many years after jejunoileal bypass surgery, and therefore, the patients should remain under strict medical supervision indefinitely.

Topics: Female; Humans; Ileum; Jejunum; Liver Cirrhosis; Middle Aged; Night Blindness; Obesity; Postoperative Complications; Reoperation; Vitamin A; Vitamin K

Factor VII activity and factor VII cross-reacting material (CRM) in plasma of patients with liver cirrhosis have been studied before and after vitamin K1 parenteral administration. Subjects were divided into two groups according to the absence (group I) or the presence (group II) of the following clinical findings: ascites, portal hypertension, encephalopathy. Factor VII activity and CRM show a statistically significant correlation (p less than 0.001) in all patients. In group II, significantly reduced levels of both activity and CRM were found as compared to the reference and the group I values. No variations were found after vitamin K administration. Different thromboplastins, investigated with respect to their sensitivity for factor VII, acted differently. Patients with normal albumin levels also showed normal levels of factor VII activity and antigen. No correlation was found in group II. The data discussed suggest that in liver cirrhosis with unknown aetiology no immunologically detectable precursor of factor VII is present.

Topics: Adult; Aged; Blood Coagulation Disorders; Cross Reactions; Factor VII; Female; Humans; Isoantigens; Liver Cirrhosis; Male; Middle Aged; Prothrombin Time; Serum Albumin; 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

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

Topics: Anti-Bacterial Agents; Blood Transfusion; Emergencies; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Microcirculation; Portacaval Shunt, Surgical; Prognosis; Therapeutic Irrigation; Time Factors; Vitamin K

Topics: Arteriosclerosis; Female; Humans; Hypertension; Liver Cirrhosis; Male; Neoplasms; Rheumatic Diseases; Vitamin K

Topics: Blood Coagulation Disorders; Humans; Liver Cirrhosis; Male; Middle Aged; Prothrombin; Vitamin K

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

Topics: Acute Disease; Adolescent; Adult; Aged; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Blood Coagulation Tests; Chemical and Drug Induced Liver Injury; Child; Cholesterol; Fatty Liver; Female; gamma-Globulins; Halothane; Hepatitis A; Humans; Indicators and Reagents; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Male; Methods; Middle Aged; Serum Albumin; Vitamin K

Topics: Adult; Angiography; Heparin; Hepatitis B; Humans; Liver Cirrhosis; Male; Portal System; Splenectomy; Splenic Vein; Thrombophlebitis; Vitamin K

Topics: Acute Disease; Blood Coagulation Disorders; Heparin; Humans; Liver Cirrhosis; Vitamin K

Topics: Adolescent; Adult; Aged; Celiac Disease; Feces; Female; Humans; Intestinal Absorption; Lipid Metabolism; Liver Cirrhosis; Male; Middle Aged; Vitamin K

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

Topics: Antifibrinolytic Agents; Ascorbic Acid; Blood Coagulation Disorders; Hemostatics; Humans; Liver Cirrhosis; Vitamin K

Topics: Adult; Female; Fetus; Humans; Liver Cirrhosis; Prednisolone; Pregnancy; Pregnancy Complications; Prognosis; 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: Humans; Hypoprothrombinemias; Liver Cirrhosis; Male; Middle Aged; Vitamin K

Topics: Blood Coagulation Disorders; Factor V; Factor VII; Factor X; Hemorrhage; Humans; In Vitro Techniques; Liver Cirrhosis; Prothrombin; Vitamin K

Topics: Alcoholism; Antifibrinolytic Agents; Bilirubin; Blood; Drug Therapy; Hematologic Tests; Humans; Infusions, Parenteral; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Function Tests; Prothrombin; Serum Albumin; Vitamin K; Vitamin K 1; Vitamins

Topics: Electrophoresis; Humans; Leukemia; Liver Cirrhosis; Neoplasms; Pyridoxine; Vitamin A; Vitamin K; Vitamins

Topics: Ascites; Diet; Diet Therapy; Diuretics; Drainage; Humans; Liver Cirrhosis; Rest; 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: 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

Topics: Antifibrinolytic Agents; Beriberi; Humans; Liver Cirrhosis; Male; Pathology; Pellagra; Physiology; Porphyrias; Retinoids; Riboflavin; Thiamine; Vitamin K

Topics: Blood Transfusion; Esophageal and Gastric Varices; Esophagoscopy; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Pituitary Hormones, Posterior; Portography; Splenectomy; Surgical Procedures, Operative; Vasopressins; Vitamin K

Topics: Adrenal Cortex Hormones; Alcoholism; Arginine; Diet; Diet Therapy; Diuretics; Folic Acid; Glutamates; Humans; Lipotropic Agents; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Extracts; Malates; Pterins; RNA; Spironolactone; Sulfonamides; Vitamin B Complex; Vitamin K

Topics: Anticoagulants; Ascites; Diet, Sodium-Restricted; Diuretics; Edema; Humans; Hydroflumethiazide; Liver Cirrhosis; Neomycin; Organomercury Compounds; Spironolactone; Vitamin K; Vitamins

Topics: Humans; Hypoprothrombinemias; Liver Cirrhosis; Nutrition Therapy; Prothrombin; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Humans; Hypoprothrombinemias; Liver Cirrhosis; Naphthoquinones; Prothrombin; Vitamin K; Vitamin K 1

Topics: Biopsy; Fatty Liver; Humans; Liver Cirrhosis; Vitamin A; Vitamin K; Vitamins

Topics: Antifibrinolytic Agents; Heparin Antagonists; Humans; Hypoprothrombinemias; Liver Cirrhosis; Naphthoquinones; Prothrombin; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Factor Xa; Humans; Jaundice; Jaundice, Obstructive; Liver Cirrhosis; Naphthoquinones; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Humans; Liver Cirrhosis; Naphthoquinones; Retinoids; Vitamin K

Topics: Antifibrinolytic Agents; Ascites; Hemostatics; Humans; Liver Cirrhosis; Vitamin K

Topics: Antifibrinolytic Agents; Humans; Liver Cirrhosis; Naphthoquinones; Retinoids; Vitamin K

Topics: Antifibrinolytic Agents; Humans; Liver Cirrhosis; Naphthoquinones; Retinoids; Vitamin K; Vitamins