Hepatitis Immune reaction

A rare but serious event that can result from irreversible CYP inhibition is the development of a hypersensitivity reaction. The bioactivation of a drug and the formation of a covalent adduct between the activated substrate and the enzyme can lead to hapten formation and eventually to an idiosyncratic autoimmune response (usually in the form of autoimmune hepatitis) [14]. The hapten formation is the first key step toward the autoimmune response. The CYP macromolecule is made immunogenic ( foreign ) by the covalent binding of the electrophilic metabolites, and the immune reaction follows with the production of autoantibodies against the target molecule (not necessarily alkylated). 

The authors noted that thrombotic microangiopathy due to cocaine is fairly rare. Its pathogenesis is unclear, possible mechanisms being an immune reaction or direct damage to the vascular endothelium. Cocaine-induced acute hepatitis has been linked to several toxic metabolites, including norcocaine and N-hydroxynorcocaine, which are produced by cytochrome P450 enzymes. 

Hepato toxicity Liver, bile duct, and gall bladder. The liver is particularly susceptible to xenobiotics due to its large blood supply and its role in metabolism Steatosis (lipid accumulation in hepatocytes) Chemical hepatitis (inflammation of the liver) Hepatic necrosis (death of the hepatocytes) Hepatic cancer (cancer of the liver) Hepatic cirrhosis (chronic fibrosis) Hypersensitivity (immune reaction resulting in hepatic necrosis)... 

Only an efficient antiyiral immune reaction can eliminate the hepatitis C virus. In cases of acute HCV infection, minimal (endogenous) interferon-a values are detectable in the serum, i.e. the virus effects a poor interferon induction in the organism. The CD8+ and CD4 T lymphocytes appear to be mainly responsible for virus elimination. The problems of HCV infection lie in the fact that the patient has virtually no chance of spontaneous improvement or even healing with a chronic course of disease, i.e. there is practically no self-limiting factor in a disease process that has become chronic. 

Hepatic damage related to isoflurane anesthesia has very occasionally been described (9,10), including one report of hepatic necrosis and death (11). Hepatitis or hepatocellular injury has been described with all current volatile anesthetics. Among these, halothane-associated hepatitis has been best characterized and is probably caused by an immune reaction induced by hepatocyte proteins that have been covalently trifluoroacetylated by the trifluoro-acetyl metabolite of halothane. The reactive acyl-halide metabolite of trifluoroacetic acid can trifluoroacetylate liver proteins, resulting in immune-mediated hepatic necrosis (12). However, isoflurane biotransformation to trifluoroacetate is less than 0.2%, compared with 15-20% for halothane. 

Approximately 60-80% of halothane taken up by the body is eliminated unchanged via the lungs in the first 24 hours after its administration. A substantial amount of the halothane not eliminated in exhaled gas is biotransformed by hepatic CYPs. Trifiuoroacetylchloride, an intermediate in oxidative metabolism of halothane, can trifluoroacetylate several proteins in the liver. An immune reaction to these altered proteins may be responsible for the rare cases of fulminant halothane-induced hepatic necrosis. 

A frequent mechanism of DILI is the metabolic activation of drugs by cytochrome P450 (CYP) into chemically reactive, electrophilic metabolites, which react with and covalently bind to hepatic proteins and glutathione (Pessayre 1995). These reactive metabolites can trigger hepatitis through direct toxicity or immune reactions (Robin et al. 1997 Pessayre et al. 1999). 

Ipilimumab (Yervoy) CTLA-4 2011 Not conducted Not conducted 6-month monkey No oigan toxicity 1 antibody response to viral vaccine challenge Immune-mediated adverse reactions due to T-cell activation and proliferation. Immune-mediated hepatitis, immune-mediated endocrinopathies ... 

Vaccine diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus combined Pediarix Active immunization against diphtheria, tetanus, pertussis and all known subtypes of hepatitis B virus, and poliomyelitis immunization Sfee adverse reactions against individual vaccines. Primary immunization series 3 doses of 0.5 mLat 6-to 8-week intervals IM (first dose is 2 months of age, but may be given as early as 6 weeks of age)... 

Agents targeting the excessive immune response or cytokines involved in IBD are potential treatment options (Table 16-3). Azathioprine and its active metabolite 6-mercaptopurine (6-MP) are inhibitors of purine biosynthesis and reduce IBD-associated GI inflammation. They are most useful for maintaining remission of IBD or reducing the need for long-term use of corticosteroids. Use in active disease is limited by their slow onset of action, which may be as long as 3 to 12 months. Adverse effects associated with azathioprine and 6-MP include hypersensitivity reactions resulting in pancreatitis, fever, rash, hepatitis, and leukopenia.25,26... 

Adverse effects. Fatigue, orthostatic hypotension, extrapyramidal Parkin-son-like symptoms (p. 88), cutaneous reactions, hepatic damage, immune-hemolytic anemia... 

Immunoglobulin obtained from pooled plasma obtained from hepatitis B and HIV negative donors is used as an aspecific immunostimulant in immunodeficiency diseases, idiopathic thrombocytopenia, autoimmune hemolytic anemias, Kawasaki syndrome and to prevent infections in immune compromised patients with leukemia or multiple myeloma. Adverse effects include potentially severe hypersensitivity reactions. 

Hepatitis B is a worldwide disease caused by the hepatitis B virus (HBV). HBV primarily affects the liver inducing an inflammatory reaction that destroys liver cells and often hinders liver function. The consequences of infection are variable and unpredictable. They depend on the age and immunity status of the patient. 

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