vitamin-k-semiquinone-radical and Liver-Failure--Acute

Paediatric acute liver failure (PALF) is defined as a biochemical evidence of acute liver injury in a child with no previous history of chronic liver disease characterised by an international normalised ratio (INR) of 1·5 or more unresponsive to vitamin K with encephalopathy, or INR of 2·0 or more with or without encephalopathy. PALF can rapidly progress to multiorgan dysfunction or failure. Although the transplant era has substantially changed the outlook for these patients, transplantation itself is not without risks, including those associated with life-long immunosuppression. Consequently, there has been an increased focus on improving medical management to prioritise bridging of patients to native liver survival, which is possible due to improved understanding of the underlying pathophysiology of multiorgan involvement in PALF. In this Review, we discuss recent advances in the medical management of PALF with an aim of reducing the need for liver transplantation. The Review will focus on the non-specific immune-mediated inflammatory response, extracorporeal support devices, neuromonitoring and neuroprotection, and emerging cellular and novel future therapeutic options.

Topics: Brain Diseases; Child; Humans; Liver Failure, Acute; Liver Transplantation; Vitamin K

Acute liver injury and acute liver failure are syndromes characterized by a rapid loss of functional hepatocytes in a patient with no evidence of pre-existing liver disease. A variety of inciting causes have been identified, including toxic, infectious, neoplastic, and drug-induced causes. This article reviews the pathophysiology and clinical approach to the acute liver injury/acute liver failure patient, with a particular emphasis on the diagnostic evaluation and care in the acute setting.

Topics: Animals; Cat Diseases; Cats; Chemical and Drug Induced Liver Injury; Diet Therapy; Dog Diseases; Dogs; Liver Failure, Acute; Prognosis; Vitamin K

Patients with acute-on-chronic liver failure show an aggravated hyperdynamic circulation. We evaluated, in a controlled manner, potential changes in systemic haemodynamics induced by the molecular adsorbent recirculating system (MARS) and the Prometheus system liver detoxification devices in a group of patients with acute-on-chronic liver failure.. Eighteen patients (51.2 +/- 2.3 years old; Child-Pugh score, 12.5 +/- 0.2; Maddrey score, 63.1 +/- 5.0; hepatic venous pressure gradient, 17.6 +/- 0.9 mmHg) with biopsy-proven alcoholic cirrhosis and superimposed alcoholic hepatitis were either treated with standard medical therapy (SMT) combined with MARS (n = 6) or Prometheus (n = 6) or were treated with SMT alone (n = 6) on three consecutive days (6 hours/session). Liver tests, systemic haemodynamics and vasoactive substances were determined before and after each session.. Groups were comparable for baseline haemodynamics and levels of vasoactive substances. Both MARS and Prometheus decreased serum bilirubin levels (P < 0.005 versus SMT), the Prometheus device being more effective than MARS (P = 0.002). Only MARS showed significant improvement in the mean arterial pressure (Deltachange, +9 +/- 2.4 mmHg versus -0.3 +/- 2.4 mmHg with Prometheus and -5.2 +/- 2.1 mmHg with SMT, P < 0.05) and in the systemic vascular resistance index (Deltachange, +131.5 +/- 46.2 dyne x s/cm5/m2 versus -92.8 +/- 85.2 dyne x s/cm5/m2 with Prometheus and -30.7 +/- 32.5 dyne x s/cm5/m2 with SMT; P < 0.05), while the cardiac index and central filling remained constant. This circulatory improvement in the MARS group was paralleled by a decrease in plasma renin activity (P < 0.05), aldosterone (P < 0.03), norepinephrine (P < 0.05), vasopressin (P = 0.005) and nitrate/nitrite levels (P < 0.02).. The MARS device, and not the Prometheus device, significantly attenuates the hyperdynamic circulation in acute-on-chronic liver failure, presumably by a difference in removal rate of certain vasoactive substances. These findings suggest conspicuous conceptual differences among the albumin dialysis devices.

Topics: Adult; Female; Hemodynamics; Humans; Liver Diseases, Alcoholic; Liver Failure, Acute; Male; Middle Aged; Renal Dialysis; Vitamin K

Topics: Acetylcysteine; Anemia, Aplastic; Antilymphocyte Serum; Bilirubin; Child; Cyclosporine; Female; Humans; Immunosuppressive Agents; Liver Failure, Acute; Methylprednisolone Hemisuccinate; Platelet Transfusion; Prednisone; Transaminases; Treatment Outcome; Vitamin K

We report a case of successful pregnancy outcome following maternal intravenous immunoglobulin treatment in a woman with previous history of recurrent fetal hydrops secondary to perinatal haemochromatosis.. A 32-year old woman had two successive pregnancies complicated by fetal hydrops and perinatal deaths. Pathological examination of the fetus showed severe liver destruction with siderosis of hepatocytes at extrahepatic sites, but sparing of the reticulo-endothelial elements, consistent with the diagnosis of perinatal haemochromatosis. In the subsequent pregnancy, maternal intravenous immunoglobulin was administered weekly from the 18th week of gestation until delivery by elective caesarean section at 38 weeks. The infant was treated with desferrioxamine, N-acetylcysteine, vitamins K and E.. The infant was born in good health, but had high serum ferritin levels, markedly elevated percent transferrin saturation, and mild transient derangement of liver and coagulation function. The infant made an excellent recovery and the treatment was stopped at 7 weeks of age. The liver and coagulation parameters and the serum ferritin levels returned to normal values.. Haemochromatosis should be considered in the differential diagnosis of hydrops fetalis. The recurrence risk is high, and immunomodulation with intravenous immunoglobulin treatment appears to alter the course of the disease with better infant survival.

Topics: Acetylcysteine; Adult; Deferoxamine; Diagnosis, Differential; Female; Ferritins; Fetal Diseases; Free Radical Scavengers; Gestational Age; Hemochromatosis; Humans; Hydrops Fetalis; Infant, Newborn; Live Birth; Liver Failure, Acute; Pregnancy; Recurrence; Treatment Outcome; Vitamin E; Vitamin K