Autoimmune hepatitis in the context of systemic lupus erythematosus: A narrative review of overlap syndrome and lupus-associated hepatitis

Table 2 Treatment agents for autoimmune hepatitis-systemic lupus erythematosus overlap syndrome: Doses, evidence levels, and overlap-specific considerations

Agent	Dose/regimen	Level of evidence	Role in SLE	AIH-SLE overlap considerations
First-line therapy
Prednisone/prednisolone	40-60 mg/day induction; taper over 4-6 months	RCTs; guideline-recommended (AASLD 2019, EASL 2025)	Used for SLE flares (lower doses)	AIH induction doses (0.5-1 mg/kg/day) exceed typical SLE doses; dual-purpose in overlap
Azathioprine	1-2 mg/kg/day; introduce after 2-week steroid trial	RCTs; guideline-recommended	Steroid-sparing for SLE	TPMT genotyping mandatory before initiation. Standard dual-purpose steroid-sparing agent. Safe in pregnancy (limited teratogenicity data in humans)
MMF	2-3 g/day	First-line AIH: RCT (Snijders et al[32], 2024); meta-analysis (2025). First-line lupus nephritis: Multiple RCTs	First-line for lupus nephritis (class III-V); widely used for SLE	Preferred dual-purpose agent: Superior to azathioprine for AIH remission induction (CBR OR: 2.56; SAE OR: 0.15). Absolutely contraindicated in pregnancy (category X)
Budesonide	9 mg/day + azathioprine	RCT (HIBI trial)	Not used in SLE	Alternative to prednisone for non-cirrhotic patients; reduced systemic side effects. Contraindicated in cirrhosis
Second-line/rescue therapy
Tacrolimus	1-3 mg twice daily; trough 3-5 ng/mL	Retrospective cohorts; meta-analyses	Off-label SLE	Aminotransferase normalisation in 73%-92%. Side effects (approximately 25%): Tremors, headaches, nephrotoxicity. Monitor renal function in concurrent lupus nephritis
Ciclosporin A	2-5 mg/kg/day in divided doses	Retrospective cohorts	Off-label SLE	May be preferred over tacrolimus in diabetic patients. Higher risk of hypertension and nephrotoxicity with long-term use
Voclosporin	23.7 mg twice daily + MMF	FDA-approved for lupus nephritis (AURORA trials); no AIH data	FDA-approved for active lupus nephritis	Theoretically attractive dual-purpose calcineurin inhibitor for AIH-SLE overlap. No data in AIH. Expert opinion only
6-mercaptopurine	0.75-1.5 mg/kg/day	Retrospective multicenter cohort	Off-label	Alternative in azathioprine-intolerant patients (gastrointestinal intolerance); comparable complete biochemical response to MMF but lower tolerability (67% vs 89%)
Biologic and experimental therapies
Rituximab (anti-CD20)	375 mg/m2 × 4 or 1000 mg × 2	Systematic review (n = 80, 27 studies; 2025)	Refractory SLE (off-label; EXPLORER/LUNAR trials did not meet primary endpoints)	Complete remission in 55%; partial remission in 11% in refractory AIH. AASLD: Insufficient evidence for second-line use. Infectious complications in approximately 8%
Belimumab (anti-BAFF)	10 mg/kg IV monthly or 200 mg SC weekly	FDA-approved for SLE/lupus nephritis; case series for AIH	FDA-approved for active SLE and lupus nephritis	Case series suggest laboratory improvement in AIH. Anti-BAFF mechanism targets shared B-cell pathway. No hepatotoxicity in SLE trials. No prospective data in AIH-SLE overlap
Anifrolumab (anti-IFNAR1)	300 mg IV every four weeks	FDA-approved for SLE (TULIP-1/2 trials); no AIH data	FDA-approved for moderate-to-severe SLE	Targets type I IFN pathway (dominant in SLE, not in AIH). Theoretical risk of impaired innate antiviral liver immunity. No data in AIH-SLE overlap. Monitor liver function tests
Hydroxychloroquine	200-400 mg/day	EULAR 2023 grade A for all SLE patients	Cornerstone SLE therapy: Reduces flares, organ damage, thrombosis	Continue in all AIH-SLE overlap patients. LiverTox score D: Rare cause of toxic hepatitis. Document temporal withdrawal response if DILI suspected
Low-dose IL-2	0.5-3 × 106 IU SC every five days (investigational)	Phase I trials; case series	Investigational for SLE (regulatory T-cell expansion)	Selectively expands regulatory T cells; laboratory improvement in small refractory AIH cohorts. Mechanistically rational for overlap given profound regulatory T-cell impairment documented in AIH-SLE

AIH: Autoimmune hepatitis; SLE: Systemic lupus erythematosus; RCT: Randomised controlled trial; HIBI: Hepatology Inflammatory Bowel Disease (trial); AASLD: American Association for the Study of Liver Diseases; EASL: European Association for the Study of the Liver; TPMT: Thiopurine methyltransferase; MMF: Mycophenolate mofetil; CBR: Complete biochemical response; OR: Odds ratio; SAE: Serious adverse event; FDA: Food and Drug Administration; AURORA: A Study of Voclosporin in Lupus Nephritis; BAFF: B-cell activating factor; EXPLORER: Exploratory Phase II/III SLE Evaluation of Rituximab; LUNAR: Lupus Nephritis Assessment with Rituximab; IV: Intravenous; SC: Subcutaneous; IFNAR1: Interferon-α/β receptor 1; TULIP: Treatment of Uncontrolled Lupus via the Interferon Pathway; IFN: Interferon; EULAR: European League Against Rheumatism; DILI: Drug-induced liver injury; LN: Lupus nephritis.