Recurrent Drug-Induced Liver Injury (DILI) with different drugs in the Spanish Registry: The dilemma of the relationship to autoimmune hepatitis

• Published in: Journal of hepatology Vol. 55; no. 4; pp. 820 - 827
• Main Authors: Lucena, M.I, Kaplowitz, N, Hallal, H, Castiella, A, García-Bengoechea, M, Otazua, P, Berenguer, M, Fernandez, M.C, Planas, R, Andrade, R.J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-10-2011; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents - adverse effects; Anti-Infective Agents - adverse effects; Anticholesteremic Agents - adverse effects; Antineoplastic Agents, Hormonal - adverse effects; Antipsychotic Agents - adverse effects; Antirheumatic Agents - adverse effects; Autoimmune hepatitis; Biological and medical sciences; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - immunology; Class effect; Cross-sensitivity; Drug induced liver injury; Drug toxicity and drugs side effects treatment; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis, Autoimmune - epidemiology; Hepatitis, Autoimmune - immunology; Hepatotoxicity; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Other diseases. Semiology; Pharmacology. Drug treatments; Rechallenge; Recurrence; Registries - statistics & numerical data; Second DILI episode; Spain - epidemiology; Toxicity: digestive system; Drug induced liver injury; DILI; ALP; drug induced idiosyncratic liver injury; Rechallenge; alanine aminotransferase; ALT; Autoimmune hepatitis; Class effect; alkaline phosphatase; Cross-sensitivity; CIOMS; Hepatotoxicity; Council for International Organizations of Medical Science; Second DILI episode; Immunopathology; Relapse; Toxicity; Autoimmune disease; Hepatic disease; Hepatitis; Sensitivity; Gastroenterology; Digestive diseases
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2010.12.041

Background & Aims Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. Methods All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. Results Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. Conclusions Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.