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

Table 1 Differential diagnosis of liver function test abnormalities in patients with systemic lupus erythematosus

Aetiology	Typical ALT level	Frequency in SLE	Key distinguishing features	Management approach
Lupus hepatitis	1-5 × ULN (95.7% of cases)	20%-30%	Correlates with SLEDAI; hypocomplementaemia; anti-ribosomal P positive in approximately 69%; responds to corticosteroids	Optimise SLE therapy; corticosteroids if active flare
DILI	Variable; often > 10 × ULN in severe DILI	30% of LFT cases	Temporal drug exposure; acute onset; resolves on withdrawal; HCQ: LiverTox score D	Identify offending drug; withdraw if possible
AIH	Often > 5 × ULN; can exceed 10 × ULN	0.6%-5% biopsy-confirmed	Anti-SMA (VG/VGT pattern); anti-SLA/LP (99% specific); IgG > 2 × ULN; interface hepatitis; portal plasma cells; fibrosis	Corticosteroids + azathioprine or MMF; liver biopsy mandatory
MASLD/fatty liver	1-3 × ULN	17.9%	Metabolic risk factors; steatosis on imaging; no AIH-specific autoantibodies	Metabolic risk factor modification
PBC	ALP/GGT predominant	2.4%	AMA positive; florid bile duct lesions on biopsy; Paris criteria for AIH-PBC overlap	Ursodeoxycholic acid ± immunosuppression for overlap
Vascular liver disease (Budd-Chiari, PVT, NRH)	Mild; ALP may predominate in NRH	Antiphospholipid antibodies in 30%-40% of SLE	Antiphospholipid antibodies; Doppler ultrasound; portal hypertension	Anticoagulation; TIPS; portal hypertension management
Macrophage activation syndrome	Markedly elevated (hyperinflammation)	0.9%-4.6% of SLE	Fever; splenomegaly; cytopenias; hyperferritinaemia; fibrinogen ↓; HScore ≥ 169	High-dose corticosteroids; anakinra; ciclosporin; haematology

ALT: Alanine aminotransferase; SLE: Systemic lupus erythematosus; ULN: Upper limit of normal; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; DILI: Drug-induced liver injury; LFT: Liver function test; HCQ: Hydroxychloroquine; AIH: Autoimmune hepatitis; SMA: Smooth muscle antibody; SLA: Soluble liver antigen; LP: Liver-pancreas; IgG: Immunoglobulin G; MMF: Mycophenolate mofetil; MASLD: Metabolic dysfunction-associated steatotic liver disease; PBC: Primary biliary cholangitis; ALP: Alkaline phosphatase; GGT: gamma-glutamyl transferase; AMA: Antimitochondrial antibody; PVT: Portal vein thrombosis; NRH: Nodular regenerative hyperplasia; TIPS: Transjugular intrahepatic portosystemic shunt.