From the Guidelines
Drug-induced autoimmune hepatitis is typically caused by an acute idiosyncratic reaction to certain medications, with minocycline and nitrofurantoin being the most common culprits, and discontinuation of the offending drug is often sufficient to resolve the disease. The management of autoimmune hepatitis beyond consensus guidelines suggests that drug-induced autoimmune-like hepatitis accounts for 9% of patients with the clinical phenotype of autoimmune hepatitis, and many other drugs, supplements, and toxins may also be culprits 1.
Key Points to Consider
- The clinical and histological features of drug-induced autoimmune-like hepatitis can assist in the diagnosis, including the presence of portal neutrophils and intracellular cholestasis 1.
- Discontinuation of the deleterious drug may be sufficient to resolve the disease, but this outcome is uncertain and possibly delayed (1–3 months) 1.
- Treatment with conventional corticosteroid therapy is associated with its own side effects and may be unnecessary in drug-induced liver injury 1.
- The EASL clinical practice guidelines for autoimmune hepatitis emphasize the importance of early recognition and treatment to improve care for affected patients, although they do not specifically address drug-induced autoimmune hepatitis 1.
- The British Society of Gastroenterology (BSG) guidelines for the management of autoimmune hepatitis provide a framework for the optimal management strategies in adults based on available published evidence, but also highlight the dearth of controlled clinical trials in recent decades 1.
Management and Treatment
- Discontinuation of the offending medication is the primary step in managing drug-induced autoimmune hepatitis, and may lead to resolution in some cases.
- Immunotherapy with corticosteroids and/or azathioprine may be necessary in some patients to control the autoimmune response.
- Treatment duration varies, with some patients needing long-term therapy similar to traditional autoimmune hepatitis.
- Early recognition is crucial as continued exposure to the triggering drug can lead to progressive liver damage and potentially liver failure.
From the Research
Drug-Induced Autoimmune Hepatitis
- Drug-induced autoimmune hepatitis (DIAIH) is a specific phenotype of drug-induced liver injury that may lead to acute liver failure requiring liver transplantation 2.
- Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins, and anti-tumor necrosis agents 2, 3, 4.
- The clinical features of DIAIH are indistinguishable from idiopathic autoimmune hepatitis (AIH), with both having positive AIH-related autoantibodies, elevated immunoglobulin G, and similar histopathological findings 2, 3.
Diagnosis and Treatment
- A high degree of clinical suspicion is required for the diagnosis of DIAIH, and it should be considered in any patient with acute or chronic elevations in liver-associated enzymes 4.
- Discontinuation of the offending drug is the essential treatment for DIAIH, and spontaneous improvement usually ensues within 1 month 3.
- Corticosteroid therapy may be required in patients with non-resolving liver injury or symptomatic severe disease, and it is almost invariably effective 2, 3, 5.
- Relapse after corticosteroid withdrawal probably does not occur in DIAIH, and its absence distinguishes drug-induced disease from classical autoimmune hepatitis 3.
Commonly Implicated Drugs
- The most commonly implicated drugs in DIAIH include alpha-methyldopa, fibrates, hydralazine, minocycline, nitrofurantoin, HMG-CoA reductase inhibitors (statins), iplimumab, and tumor necrosis factor alpha antagonists 4.
- Minocycline and nitrofurantoin are implicated in 90% of cases of drug-induced autoimmune-like hepatitis 3.
- Statins, such as atorvastatin, have also been reported to cause DIAIH 2.