Drug-induced autoimmune hepatitis: A minireview

Table 1 Studies comparing drug-induced autoimmune hepatitis and drug-induced liver injury

Ref.	a: Study population; b: Study period; c: Follow-up period	a: Definition of DIAIH; b: Causality tool assessment	No. of DIAIH cases, % of all DILI	No. of DILI cases	Key findings for DIAIH (in addition to Table 3)
Stephens et al[37], 2021, Spain	a: Prospective multicentre DILI database, n = 869; b: 1994-2018; c: Median 96-117 d in HC injury	a: Simplified AIH criteria; b: RUCAM (definite, highly probable, probable and possible)	26, 2.9%	843	Culprit drugs: Statins (31%); antimicrobials (23%)
De Boer et al[15], 2015, United States	a: National prospective DILI database (n = 1322), subgroup of DILI secondary to Nitrofurantoin, hydralazine, Minocycline and methyldopa (n = 88); b: 2004-2014; c: 6 mo, 12 mo or 24 mo until normalization of LFT	a: Autoimmune (AI) DILI–AI score based on seropositivity for AIH antibodies and raised IgG); b: RUCAM (definite, highly probable and probable)	47, 3.6%	Two groups: (a) 18 non-AI DILI due to 4 drugs; (b) 67 (reference cohort, DILI due to Augmentin, Isoniazid, Diclofenac)	Similar HLA-DRB1*03:01 (15%) and HLADRB1*04:01 (9%) percentage in patients with DILI compared to population controls from National Marrow Donor Program (12% and 9%, respectively)
Hisamochi et al[22], 2016, Japan	a: All DILI who underwent liver biopsy, n = 62; b: 1988-2010; c: Median 2290 d	a: Revised IAIHG criteria; b: RUCAM and JDD-W scale	23, NA	39	Culprit drugs: CAM (69.6%); NSAIDs (8.7%). IgG reduction in 87%. 50% (8/16) relapsed (4 not treated with steroids, 2 previously received steroids and 2 on tapering dose of steroid dosage). Median time to relapse 283 d (range, 47-1090 d). Rise in IgG with relapse
Licata et al[16], 2014, Italy	a: Single centre hospitalized patients with DILI, n =136 (44 with liver biopsy); b: 2000-2011; c: Mean 26 mo (12-84 mo), at least 1 yr after stopping immunosuppressants	a: Simplified AIH score ≥ 6; b: RUCAM (definite, highly probable, probable and possible)	12, 8.8%	124	Culprit drugs: NSAIDs (50%) - (Nimesulide/ketoprofen); Antimicrobials (25%) (Augmentin/Ceftriaxone); CAM (17%). 38.2% of all DILI patients had positive AIH antibodies but only 42.9% with positive antibodies have DIAIH. All DIAIH were treated with corticosteroids and all achieved remission at 15 mo. 58.3% (7/12) had addition of Azathioprine. One patient had a flare while on tapering prednisolone. In 41% (5/12), immunosuppressant was stopped after 2 yr, with no relapse

DIAIH: Drug-induced autoimmune hepatitis; DILI: Drug-induced liver injury; RUCAM: The Roussel Uclaf Causality Assessment Model; NSAIDs: Non-steroidal anti-inflammatory drugs; AIH: Autoimmune hepatitis; IAIHG: International AIH Group; IgG: Immunoglobulin G; CAM: Complementary alternative medicines.