Autoimmune-like hepatitis induced by drugs: Still many unanswered questions

Table 1 Indications and drugs linked to drug-induced autoimmune-like hepatitis

Drug	Therapeutic indication	Association with DI-AIH
Minocycline	Acne vulgaris, rosacea	Frequently reported in young females
Nitrofurantoin	Recurrent UTIs	Often presents with ANA and ASMA positivity
Methyldopa	Hypertension (especially in pregnancy)	Classical example of DI-AIH
Hydralazine	Hypertension, heart failure	Can induce lupus-like syndrome and DI-AIH
Statins (atorvastatin, rosuvastatin)	Hyperlipidemia	Increasingly reported; often presents with mild phenotype
Infliximab	Rheumatoid arthritis, Crohn’s disease, psoriasis	Anti-TNFα-induced AIH described in several cases
Adalimumab	Rheumatoid arthritis, psoriasis, ulcerative colitis	Rare, but documented in literature
Interferon-α	Chronic hepatitis B/C, certain cancers	May trigger or unmask autoimmune hepatitis
Tyrosine kinase inhibitors (e.g., imatinib)	CML, GIST	Rare cases reported

UTIs: Urinary tract infections; CML: Chronic myeloid leukemia; ANA: Antinuclear antibody; ASMA: Anti-smooth muscle antibody; DI-ALH: Drug-induced autoimmune -like hepatitis; TNFα: Tumor necrosis factor α; AIH: Autoimmune hepatitis; GIST: Gastrointestinal stromal tumor.

Table 2 Comparative studies assessing liver cellularity in classic autoimmune hepatitis vs drug-induced autoimmune-like hepatitis

Ref.	Design and cohort	Main histological findings
Chung et al[19], 2024	Retrospective cohort; 28 DI-ALH vs 39 idiopathic AIH cases	DI-ALH exhibited significantly fewer plasma cell aggregates (61% vs 97%, P < 0.001), more eosinophilic aggregates (18% vs 3%), and lower portal inflammation and fibrosis (mean Ishak 1.9 vs 3.5)
de Boer et al[14], 2017	Immunohistochemical profiling of autoimmune-DILI, idiopathic AIH, viral hepatitis	Infiltrates were predominantly CD8+ T cells across all groups. Idiopathic AIH showed significantly more CD20+ B cells and plasma cells compared to DILI-AILH, which had fewer of both
Tsutsui et al[27], 2020	Comparative clinicopathological study: Acute AIH vs DILI (Japan)	Acute AIH demonstrated greater lobular necrosis, hepatocellular rosettes, and dense plasma-cell infiltrates than DILI (all P < 0.01), supporting these as discriminating features
Suzuki et al[12], 2011	Histological scoring (DDWJ 2004) in AIH vs DILI	AIH scored significantly higher for portal inflammation, interface hepatitis, and plasma-cell infiltration than DILI (P < 0.012), confirming DDW-J scale’s diagnostic value. DI-ALH often showed portal-lobular inflammation
Björnsson et al[13], 2022	Systematic review of 186 DI-ALH case reports	DI-ALH often shows portal-lobular lymphoplasmacytic inflammation, hepatocyte rosettes, and focal necrosis, mirroring AIH histology

AIH: Autoimmune hepatitis; DI-ALH: Drug-induced autoimmune-like hepatitis; DILI: Drug-induced liver injury; DDW-J: Digestive Disease Week from Japan.

Table 3 Comparison of corticosteroid treatment in classic autoimmune hepatitis vs drug-induced autoimmune like hepatitis

Parameter	Classic AIH	DI-ALH
Initial steroid dose	Prednisone 30-60 mg/day (or equivalent)	Prednisone 20-40 mg/day (or equivalent)
Induction strategy	Often combined with azathioprine	Monotherapy with steroids usually sufficient
Tapering schedule	Gradual taper over months based on biochemical response	Faster taper once liver enzymes normalize
Duration of treatment	Long-term (often > 2 years, sometimes lifelong)	Short-term (typically < 6-12 months)
Need for maintenance therapy	Common (azathioprine or other immunosuppressants)	Rare; usually not required after resolution
Relapse after withdrawal	Frequent (up to 50%-80%)	Rare
Histologic recovery	Slower, often incomplete even after biochemical remission	Usually complete. Once drug is withdrawn inflammation resolves
Outcome/prognosis	Good with treatment, but risk of chronic disease or cirrhosis	Excellent prognosis; usually resolves without chronic sequelae
Lifelong monitoring needed	Yes	Case by case assessment

AIH: Autoimmune hepatitis; DI-ALH: Drug-induced autoimmune-like hepatitis.