Hepatitis, autoimmune

Contraindications to treatment include autoimmune hepatitis, decompensated liver disease, women who are pregnant or patients whose female partners are pregnant, hemoglobinopathies, creatinine clearance <50 mL/ min, hemodialysis, or ischemic cardiovascular or cerebrovascular disease. 

CYP450 antibodies leading to autoimmune hepatitis [68,69], Metabolic activation can also occur within the monocyte/macrophage and has been reported for many of the same xenobiotics (e.g., hydralazine) suggesting multiple mechanisms for xenobiotic autoimmune potential [68],... 

Vergani, D. and Mieli-Vergani, G., Autoimmune hepatitis, Minerva. Gastroenterol. Dietol., 50, 113, 2004. 

Mizutani, T., Shinoda, M., Tanaka, Y., Kuno, T., Hattori, A., Usui, T., Kuno, N., and Osaka, T., Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2, Drug Metab. Rev., 37, 235, 2005. 

Tienilic acid- and dihydralazine-induced hepatitis are associated with antibodies against Cyp 2C9 [53] and Cyp 1A2 [54, 55], respectively. These are also the same cytochrome P450s that are responsible for the formation of reactive metabolites of these two drags. Anticonvulsant hepatotoxicity is associated with antibodies against rodent Cyp 3 A and related human enzymes such as thromboxane synthase [56, 57], It is interesting to note that cytochromes P450 are often the target of autoantibodies in idiopathic autoimmune hepatitis [58],... 

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

Gough, A. et al., Minocycline induced autoimmune hepatitis and systemic lupus erythe-matosus-like syndrome, Br. Med. J., 312, 169, 1996. 

Lecoeur, S., Andre, C., and Beaune, P.H., Tienilic acid-induced autoimmune hepatitis Antiliver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9, Mol. Pharmacol., 50,326, 1996. 

Goldstein, N.S. et al., Minocycline as a cause of drug-induced autoimmune hepatitis. Report of four cases and comparison with autoimmune hepatitis, Amer. J. Clin. Pathol., 114, 591,2000. 

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). 

There are several examples of autoimmune hepatitis caused by mechanism-based inhibitors in the field of CYPs hepatitis induced by halothane (CYP2E1) [15,16], by tienilic acid (CYP2C9) [17] and by dihydralazine (CYP1A2) [18,19]. 

Autoimmune diseases such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis,... 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

Ribavirin tablets/Peginterferon alfa-2a Ribavirin tablets/peginterferon alfa-2a combination therapy is contraindicated in patients with autoimmune hepatitis and... 

Peginterferon alfa-2b Hypersensitivity to peginterferon alfa-2b or any component of the product autoimmune hepatitis decompensated liver disease. 

Autoimmune disorders Auto mmune disorders of multiple target organs have been reported postmarketing, including idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. 

Hepatotoxicity Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported rarely in postmarketing data in patients receiving infliximab. Autoimmune hepatitis has been diagnosed in some of... 

Interferons are contraindicated in individuals with autoimmune hepatitis or other autoimmune disease, uncontrolled thyroid disease, severe cardiac disease, severe renal or hepatic impairment, seizure disorders, and CNS dysfunction. Immunosuppressed transplant recipients should not receive interferons. Interferons should be used with caution in persons who have myelosuppression or who are taking myelosuppressive drugs. Preparations containing benzyl alcohol are associated with neurotoxicity, organ failure, and death in neonates and infants and therefore are contraindicated in this population. Interferons should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Contraindications History of autoimmune hepatitis or severe psychiatric disorders, hypersensitivity to alpha interferons... 

Contraindications Autoimmune hepatitis, decompensated hepatic disease... 

Contraindications Autoimmune hepatitis, creatinine clearance less than 50 ml/min, hemoglobinopathies, hepatic decompensation, hypersensitivity to ribavirin products, pregnancy, significant or unstable cardiac disease... 

There has been a single report of autoimmune hepatitis with the combination of cyproterone acetate and a progestogen (5). Similar events have been described very occasionally with other oral contraceptives and with diethylstilbestrol they are not unique to cyproterone. 

Kacar S, Akdogan M, Kosar Y, Parlak E, Sasmaz N, Oguz P, Aydog G. Estrogen and cyproterone acetate combination-induced autoimmune hepatitis. J Clin Gastroenterol 2002 35(1) 98-100. 

Autoimmune hepatitis was diagnosed in a previously healthy, 39-year-old woman 4 weeks after she started to take melatonin 3 mg at bedtime (22). 

Hong YG, Riegler JL. Is melatonin associated with the development of autoimmune hepatitis J Clin Gastroenterol 1997 25(l) 376-8. 

Two patients developed significantly abnormal liver function tests after receiving pegvisomant for 12 weeks (2,3). Transaminase activities rose to more than 10-fold the upper limits of the reference ranges and returned to normal after withdrawal. One of the two was treated for autoimmune hepatitis (5). Monitoring of liver enzymes every 4-6 weeks is recommended for 6 months or if symptoms of hepatitis develop. 

A 65-year-old woman developed fatigue, jaundice, and altered liver function tests while taking atorvastatin (20 mg/day for some weeks) (14). On the basis of clinical, serological, and histological findings, a diagnosis of autoimmune hepatitis was made. 

The authors suggested that atorvastatin may have unmasked an underlying autoimmune hepatitis. 

A patient developed atorvastatin-induced severe autoimmune hepatitis and a lupus-like syndrome. Although the drug was immediately withdrawn, the disease persisted and deteriorated to a fulminant form with acute hepatic failure. There was no response to conventional immunosuppression with glucocorticoids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery. The patient had the HLA haplotypcs DR3 and DR4, which are well-known genetic factors associated with autoimmune diseases. 

This case is the first report of drug-induced lupus-like syndrome concomitant with severe autoimmune hepatitis in a genetically predisposed patient (23). 

Pelli N. Autoimmune hepatitis revealed by atorvastatin. Eur J Gastroenterol Hepatol 2003 15 921 i. 

Graziadei IW. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus 2003 12 409-12. 

A 50-year-old woman with previous autoimmune thyroid disease taking atorvastatin developed acute hepatitis when she also was given ezetimibe (4). Further investigations, including liver biopsy, showed a probable drug-induced autoimmune hepatitis. 

Heyningen CV. Drug-induced acute autoimmune hepatitis during combination therapy with atorvastatin and ezetimibe. Ann Clin Biochem 2005 42 402-4. 

Ganne-Carrie N, de Leusse A, Guettier C, Castera L, Levecq H, Bertrand HJ, Plumet Y, Trinchet JC, Beaugrand M. Hepatites d allure auto-immune induites par les fibrates. [Autoimmune hepatitis induced by fibrates.] Gastroenterol Clin Biol 1998 22(5) 525-9. 

A 61-year-old woman developed symptoms of acute hepatitis 6 weeks after she began to take fluvastatin sodium 20 mg/day for hypercholesterolemia (3). Ultrasonography and liver biopsy confirmed the diagnosis of non-obstructive intrahepatic jaundice. Studies of viral markers and autoimmune factors excluded viral hepatitis and autoimmune hepatitis. There was a high serum concentration of a metabolite of fluvastatin, suggesting a possible anomaly of drug metabolism. All liver function tests normalized 8 weeks after the withdrawal of fluvastatin. 

Immunology. Blood tests can detect viruses and antibodies to viruses, for example hepatitis A/B virus, or auto-antibodies from autoimmune disorders of the liver, for example primary biliary cirrhosis (associated with anti-mitochondrial antibodies), autoimmune hepatitis (associated with smooth muscle antibodies) and primary sclerosing cholangitis (associated with antinuclear cytoplasmic antibodies). 

Autoimmune hepatitis If single drug therapy then start with 60 mg p.o. q.d. and taper over 4 weeks to 20 mg q.d. maintenance dose until end point. If combination therapy with azathioprine, then start with 30 mg q.d. and taper over 4 weeks to 10 mg q.d. maintenance dose until endpoint... 

Chronic Hepatitis B Chronic Hepatitis C Autoimmune Hepatitis Wilson s Disease... 

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