Autoimmune liver toxicity

Thiono and sulfhydryl drugs are also associated with a significant incidence of a lupus-like syndrome. Propylthiouracil is associated with a significant incidence of lupus [18] as well as liver toxicity [19, 20] and agranulocytosis [21], Penicillamine is associated with lupus, agranulocytosis [22] and a variety of autoimmune syndromes as discussed later. 

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],... 

Azathioprine is a cytotoxic inhibitor of purine synthesis effective for the control of tissue rejection in organ transplantation. It is also used in the treatment of autoimmune diseases. Its biologically active metabolite, mercaptopurine, is an inhibitor of DNA synthesis. Mercaptopurine undergoes further metabolism to the active antitumour and immunosuppressive thioinosinic acid. This inhibits the conversion of purines to the corresponding phosphoribosyl-5 phosphates and hypoxanthine to inosinic acid, leading to inhibition of cell division and this is the mechanism of the immunosuppression by azathioprine and mercaptopurine. Humans are more sensitive than other species to the toxic effects of the thiopurines, in particular those involving the haematopoietic system. The major limiting toxicity of the thiopurines is bone marrow suppression, with leucopenia and thrombocytopenia. Liver toxicity is another common toxic effect. 

A 39-year-old woman developed idiopathic thrombosis of the posterior tibial vein. Oral contraceptives and resistance to activated protein C were identified as risk factors. After initial treatment with intravenous heparin, she was given phenprocoumon and the oral contraceptive was withdrawn. After 4 months she developed subacute liver failure and phenprocoumon was withdrawn immediately. Autoimmune disease, viral hepatitis, toxic causes, and Budd-Chiari syndrome were excluded. Despite symptomatic treatment, she deteriorated further and orthotopic liver transplantation was performed. Histopathology of the explanted liver further excluded ischemic Uver cell necrosis and Budd-Chiari syndrome. 

A 60-year-old patient, who had taken no medications other than kava extract, developed liver and kidney failure and progressive encephalopathy (8). Viral, metabolic, and autoimmune causes were excluded. Liver biopsy was consistent with toxic Uver damage. The patient eventually received an orthotopic Uver transplant and made a good recovery. 

A 63-year-old female was on treatment with double antiplatelet medication, bisoprolol, amlodipine, atorvastatin and ranolazine due to a previous medical history of hypertension and unstable angina with no signs of myocardial damage. At 3 months, she began to experience malaise and insomnia. A biochemical study showed an increase in liver function parameters. The most common viral and autoimmune causes were ruled out. Laboratory results pointed towards a hepatocellular toxic-medication source. After cessation of ranolazine the patient was asymptomatic and normalisation of liver function tests was achieved [35]. 

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