Prophylactic histamine 2 blockers or proton-pump inhibitors should be started to all patients requiring mechanical ventilation [31]

Prophylactic histamine 2 blockers or proton-pump inhibitors should be started to all patients requiring mechanical ventilation [31]. thioctic acid (300?mg/kg/day)Galactosaemia/hereditary fructose intolerance: removal dietHereditary tyrosinaemia: NTBC (0.5?mg/kg bd)?+?removal dietHaemophagocytic lymphohistiocytosis:?Chemotherapy haematopoietic stem cell transplantation (familial/genetically verified and persistent/reactivation of secondary HLH)Neonatal haemochromatosis:?Double volume exchange transfusion and intravenous immunoglobulin (1?g/kg) Open in a separate windows (Reproduced with permission from Shanmugam et al., Acute liver failure in children: Management protocol, manual of paediatric liver intensive care) (Springer publication in print) Drugs and Toxins In developed countries drugs and toxins have become the most common identifiable cause of drug-induced acute liver failure in adults and children. Drug-induced liver injury (DILI) can be a dose-dependent response, an idiosyncratic reaction or a synergistic reaction when two medications are given together. It is essential to enquire about any indigenous/herbal medicine intake as some are potentially hepatotoxic [7]. Acetaminophen is the most common drug associated with ALF and is normally a Faropenem sodium dose-dependent hepatotoxic agent. Acetaminophen is usually detoxified mainly by glucuronidation (40%), sulphation (20C40%) and N-hydroxylation (15%). A small fraction is usually metabolized via cytochrome P450 to yield em N /em -acetyl-para-benzoquinone-imide (NAPQI), a harmful intermediate compound which irreversibly conjugates with the sulphhydryl group of glutathione and causes hepatocyte necrosis [8]. NAPQI forms acetaminophen-protein adducts, which acts as a specific biomarker for chronic acetaminophen-related toxicity. In acute acetaminophen poisoning, serum levels after 4?h of ingestion are useful in identifying high-risk patients. Genetic polymorphism of cytochrome P450 isoenzymes could predispose affected people to acetaminophen toxicity. Anti-tuberculosis drugs, particularly isoniazid, are associated with drug-induced ALF. The mechanism of toxicity is similar to acetaminophen; oxidation via cytochrome P450 pathway results in toxic metabolites. The true incidence of idiosyncratic drug-induced liver injury (DILI) is usually unknown; reports have suggested to up to 14 new cases/100,000/12 months [9]. Around 8% of idiosyncratic DILI developed ALF Faropenem sodium [10]. DILI is usually unpredictable, but genetic susceptibility of an individual to certain drugs and underlying mitochondrial cytopathies are proposed causes [11]. The Councils for International Businesses of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) level is helpful in establishing causal relationship between offending drug and liver damage. Using the scoring system, suspected drug could be categorized into definite or highly probable (score? ?8), probable (score 6C8), possible (score 3C5), unlikely (score 1C2) and excluded (score??0) [12]. This level is helpful in identifying drug-induced hepatotoxicity even in newly marketed drugs and for a previously unreported older drug. Chemotherapy drugs are known to produce veno-occlusive disease leading on to ALF due to endothelial damage. Few of the common drugs that cause ALF are layed out in Table 8.2. Viral Hepatitis Water-borne viral hepatitis (hepatitis A and E) is the most common cause of ALF in developing countries with poor sanitation facilities. Following contamination Faropenem sodium with hepatitis A computer virus, the risk of developing liver failure is usually 0.1C0.4%, and this further increases with underlying chronic liver Snap23 disease. Faropenem sodium Usually the disease runs a benign course with spontaneous recovery, but some might require liver transplantation [13]. With hepatitis E contamination, the risk of developing ALF in adults is usually 0.6C2.8% [14]. Recent evidence suggests that case fatality due to hepatitis E-induced ALF in pregnancy is similar to that of age-matched general populace [15]. The ALF due to hepatitis B computer virus (HBV) can occur at the time of acute contamination, reactivation of chronic HBV contamination or seroconversion from a hepatitis B e antigen-positive to a hepatitis B e antibody (HBeAb)-positive state. Superinfection or co-infection of HBV-infected patients with hepatitis delta computer virus (HDV) can cause liver failure. Hepatitis C computer virus (HCV) infection has not been reported as a cause of ALF, and herpes simplex virus can cause ALF, of which Faropenem sodium herpes simplex virus 1 and 2 (HSV) is the predominant cause of.