Immunosuppressant drugs hepatitis

Corticosteroids. Corticosteroids are immunosuppressant drugs which have had beneficial effects in autoimmune chronic active hepatitis. They were investigated for the treatment of ehronic aetive hepatitis B (183-185), resulting in increased HBV replication, membrane expression of viral antigen, and delayed HBeAg seroconversion (132, 186). Stopping steroid treatment usually leads to a rebound in hepatic disease activity but may be followed by termination of viral replication within a few months (187). Thus, despite the decrease in transaminase activity, corticosteroids have little role in the treatment of chronic hepatitis B. However, corticosteroids may be useful for pretreatment of certain patients prior to interferon therapy (188) or for enhaneing the efficacy of interferon or adenine arabinoside (ARA-A) treatment by prior steroid withdrawal in patients with mild inflammatory activity (189). 

The antibody response to hepatitis A vaccine in patients taking immunosuppressants after organ transplantation is variable, " and declines quicker than in healthy controls. In renal transplant recipients, there is some evidence that the response is inversely related to the number of immunosuppressant drugs. ... 

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information needed for the follow-up of the patient. Liver transplantation-excess mortality, graft loss, and hepatic artery thrombosis (HAT) The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death. 

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. 

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. 

Cyclosporin A, a fungal metabolite, is a cyclic polypeptide that consists of 11 amino acids. It has a biologic half-life of 4 to 6 h and displays a preferential T cell cytotoxic property, in that it inhibits the factors that stimulate T lymphocyte proliferation. Cyclosporin A has been used as the sole immunosuppressant (without prednisone or other drugs) for cadaveric transplants of the kidney, pancreas, and liver. Cyclosporin A has been observed to cause reversible hepatic toxicity and nephrotoxicity. 

Immunosuppressive therapy is currently an option in chronic severe asthma, where cyclosporine seems to be an effective drug and rapamycin promises to be another alternative. Tacrolimus is currently under clinical investigation for the management of autoimmune chronic active hepatitis... 

Three adolescents taking therapeutic doses of minocycline for 12-20 months met the 1993 International Autoimmune Hepatitis Group criteria for autoimmune hepatitis. All had hypogammaglobulinemia and positive antinuclear antibody and antismooth muscle antibody titers. Two underwent liver biopsy that showed severe chronic lymphoplasmocytic inflammation, necrosis, and fibrosis. All other causes of liver disease were excluded. One patient had resolution of symptoms after withdrawal of the drug, while two required immunosuppressive therapy. 

Mycophenolate mofetil (Cellcept) is an immunosuppressant approved for prophylaxis of organ rejection in patients with renal, cardiac, and hepatic transplants. Myco-phenolic acid, the active derivative of mycophenolate mofetil, inhibits the enzyme inosine monophosphatase dehydrogenase (IMPDH), thereby depleting guanosine nucleotides essential for DNA and RNA synthesis. Moreover, mycophenolic acid is a fivefold more potent inhibitor of the type 11 isoform of IMPDH found in activated B- and T-lymphocytes and thus functions as a specific inhibitor of T- and B-lymphocyte activation and proliferation. The drug also may enhance apoptosis. 

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