What Drugs Can Trigger Autoimmune Hepatitis?
The etiology of autoimmune hepatitis is undefinable, but the disease can be triggered in vulnerable persons by an external factor, such as viruses, drugs or herbal medicines. The drug-induced autoimmune liver disease is a poorly defined and most often it is considered as an underestimated liver disease. A small number of drug-induced liver injury cases can exhibit features typical of autoimmune hepatitis. Many drugs have been linked to autoimmune hepatitis phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity.
Three Clinical Settings of Drug-Induced Autoimmune Liver Disease
Based on the drug-induced autoimmune liver disease, three clinical settings have been proposed
- Autoimmune hepatitis with drug-induced liver injury,
- drug-induced autoimmune hepatitis, and
- Immune-mediated drug-induced liver injury.
In addition, there are occurrences of mixed features like drug-induced autoimmune hepatitis and immune-mediated drug-induced liver injury. Sometimes positive autoantibodies are seen in drug-induced liver injury cases.
What Drugs Can trigger Autoimmune Hepatitis?
What are the drugs involved in triggering AH? Many clinical observations suggest that drugs are potential triggers in some patients. Several drugs have been identified to cause autoimmune hepatitis that may persist after discontinuation, suggesting that they triggered true autoimmunity. Oxyphenisatin, nitrofurantoin, minocycline, chlometacin, chlorpromazine, halothane, hydralazine, and alpha-methyl dopa can trigger autoimmune hepatitis. It is interesting to note that drug-metabolizing enzymes of phase I and phase II are common targets of autoimmunity in idiopathic autoimmune hepatitis and viral hepatitis.
Other Drugs Involved in Liver Injury
Nowadays, more than 900 drugs, toxins, and herbal remedies have been reported to cause liver injury. Recently, it has been reported that at least 24 drugs, probably more, have been associated with autoimmune chronic hepatitis mimicking autoimmune hepatitis. With the appearance of new statins, biologic agents, and antibiotics, it will be quite normal to see more new agents being reported as being responsible for new drug-induced autoimmune hepatitis cases. Infliximab, adalimumab, etanercept, efalizumab, ipilimumab, atomoxetine, diclofenac, fenofibrate, pemoline, phenprocoumon, dihydralazine, tielinic acid, and benzarone reported as being responsible for new drug-induced autoimmune hepatitis case. Elderly individuals have an increased risk of drug toxicity. The risk of drug-induced liver injury increases with age for certain drugs, such as those that are implicated in autoimmune-like hepatitis (nitrofurantoin, halothane, and isoniazid).
Risk Factors for Drug-Induced Autoimmune Hepatitis
The risk factors for drug-induced autoimmune-like hepatitis are unpredictable. The factors that may affect drug-taking behavior as well as host-specific genetic and metabolic disturbances may affect drug handling. Socio-economic, psychological, and cultural issues can influence the type, frequency, and duration of treatment, and certain diseases with propensities for a particular gender or age group may skew the perception of risk. The major risk factors implicated in idiosyncratic drug-induced liver injury are old age, gender, dose, drug interactions, cross-sensitization, genetic factors, and hepatic metabolism of the compound.
Management of Drug-Induced Autoimmune Hepatitis
Generally, a short course of immunosuppressive treatment is sufficient for a patient with drug-induced autoimmune hepatitis. All were treated with corticosteroids and remission was achieved after six months in 10 of the cases.
Oxyphenisatin, nitrofurantoin, minocycline, chlometacin, chlorpromazine, halothane, hydralazine, and alpha-methyl dopa can trigger autoimmune hepatitis. More than 90% of these drug-induced autoimmune hepatitis cases were associated with two drugs, nitrofurantoin, and minocycline. The risk factors for drug-induced autoimmune-like hepatitis are unpredictable (idiosyncratic). Old age, gender, dose, drug interactions, cross-sensitization, genetic factors, and hepatic metabolism of the compound may be the risk factor associated with idiosyncratic cases. These cases were easily manageable with corticosteroids and diminution of diseases is noted after six months.
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