Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

Table 1 Classification of drug-induced autoimmune liver disease

AIH with DILI	Patients with known AIH AIH quiescent: the drug may be the trigger of a new bout AIH under IS or corticosteroids treatment: Reactivation of known AIH upon intro duction of a newdrug (very difficult to demonstrate a causal relationship as it might be coincidental Often advanced fibrosis on histology
DI-AIH	Patients with a low grade disease not diagnosed before or predisposition to AIH Drug produce an immune reaction that lead to a chronic process: Perpetuating the AIH Permanent need of IS Habitually typical HLA-DR associated
IM-DILI (Autoimmune hypersensitivity)	Fever, eosinophilia, lymphadenopathy, rush Indistinguishable from true AIH: Mandatory IS treatment Frequently spontaneous remission after drug cessation Usually complete response to treatment and sustained remission without relapse It is the most frequent drug-induced immune process in the liver attributable to drugs
Mixed autoimmune type	Patients with mixed clinical features of DI-AIH and IM-DILI Complete response to IS treatment but with chronic course after withdrawal Patients under IS treatment for another autoimmune disease. Withdraw IS drugs is not possible. Remission cannot be evaluated
DILI with positive autoantibodies	Patients with positive autoantibodies The probability of developing DIAILD increases in second DILI episodes indepe dently of the causal agent

AIH: Autoimmune hepatitis; DILI: Drug-induced liver injury; IS: Immunosuppressants; IM-DILI: Immunomediated DILI; DIAILD: Drug-induced autoimmune liver disease; HLA: Human leukocyte antigen.

Table 2 Elements to be reported when a case of drug- induced autoimmune liver disease is suspected

Previously obtained ANA

Evolution:

During the treatment with the suspicious drug

After drug withdrawal

Check for the presence of HLA-DR:

HLA-DRB1*0301,0401,07,1301

Drug type

Time to onset from the beginning of the treatment

AIH diagnosed:

During the course of treatment

After withdrawal of the drug

AIH scales for diagnosis

International autoimmune hepatitis group report (4)

Simplified score (5)

Previous DILI episodes

Response to corticosteroids

Autoimmune titres evolution

IgG values evolution

AIH: Autoimmune hepatitis; DILI: Drug-induced liver injury.

Table 3 Drugs and drug-induced autoimmune liver disease

Well stablished drugs:

Minocycline

Nitrofurantoin

Oxyphenisatin, alpha-methyl-dopa, clometacin.

Emerging drugs:

Statins

Biologics agents:

Infliximab

Others: adalimumab, etanercept, efalizumab, ipilimumab

Other drugs:

Less compelling association (infrequent reports): atomoxetine, diclofenac, fenofibrate, pemoline, phenprocoumon, dihydralazine, tielinic acid, benzarone