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

Table 4 Mechanistic and clinical distinctions between autoimmune hepatitis and lupus hepatitis

Feature	Autoimmune hepatitis	Lupus hepatitis
Pathomechanism
Primary mechanism	Cell-mediated; CD4+ Th1/Th17 and CD8+ CTL-driven hepatocyte injury via perforin/granzyme and Fas/FasL	Humoral; immune complex deposition → complement activation → Kupffer cell/macrophage/NK cell recruitment
Type I IFN signature	Absent; NLRP3 inflammasome dominates	Prominent; pDC activation via TLR7/9 → IFN-α
Treg function	Moderately impaired; ↓ CD39+ Tregs; defective AHR signalling; failed IL-17 suppression	Moderately impaired; overlap group shows most severe impairment (↓ FOXP3, ↑ IFN-γ+, Th1 skewing)
Serological markers
ANA	80% positive; not discriminatory	95%-99% positive; not discriminatory
Anti-SMA (VG/VGT)	63% positive; VG/VGT pattern strongly favours AIH	Approximately 4.4% positive; low
Anti-SLA/LP	14%-20%; 99% specific for AIH	Not reported in lupus hepatitis
Anti-ribosomal P	0% in primary AIH	68.8% in lupus hepatitis; OR approximately 5.4 for hepatic SLE involvement
Serum C3/C4	Normal or elevated	Consumed (hypocomplementaemia)
Histological features
Hallmark pattern	Interface hepatitis; portal lymphoplasmacytic infiltrate; plasma cells (66%); hepatocyte rosettes; emperipolesis	Non-specific mild lobular hepatitis; no plasma cell predominance; minimal portal inflammation
C1q immunofluorescence	Negative (0%)	Positive in 70% of biopsies (P = 0.011 vs non-lupus controls)
Fibrosis	Common: F3/F4 in 28%-33% at presentation	Rare; cirrhosis essentially absent in isolated disease
Clinical features and outcomes
Typical ALT level	Often > 5 × ULN	1-5 × ULN (95.7% of cases)
Response to corticosteroids	Dramatic but incomplete without steroid-sparing agent; relapse common on withdrawal	Typically rapid and complete; steroid-sparing agent not required
Long-term prognosis	Cirrhosis in 28%-33%; SMR: 1.63; liver transplantation possible	Excellent; liver-related mortality essentially absent

CTL: Cytotoxic T lymphocyte; NK: Natural killer; IFN: Interferon; LRP3: NLR family pyrin domain containing 3; pDC: Plasmacytoid dendritic cell; TLR: Toll-like receptor; AHR: Aryl hydrocarbon receptor; IL: Interleukin; FOXP3: Forkhead box P3; ANA: Antinuclear antibody; SMA: Smooth muscle antibody; AIH: Autoimmune hepatitis; SLA: Soluble liver antigen; LP: Liver-pancreas; OR: Odds ratio; SLE: Systemic lupus erythematosus; ALT: Alanine aminotransferase; ULN: Upper limit of normal; SMR: Standardised mortality ratio; Th: T helper; Treg: Regulatory T cell.