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

Table 6 International Autoimmune Hepatitis Group simplified scoring system for autoimmune hepatitis with systemic lupus erythematosus-specific caveats

Parameter	Criterion	Score	Caveat in SLE patients
Autoantibodies (maximum 2 points)
ANA or anti-SMA	≥ 1:40	+1	ANA is present in ≥ 95% of SLE patients → virtually all SLE patients score ≥ 1 point by default, inflating the score
ANA or anti-SMA	≥ 1:80	+2	High-titre ANA is the rule in SLE; assigns 2 points without discriminatory value
Anti-LKM1	≥ 1:40	+2	Rare in SLE; if present, strongly favours type 2 AIH
Anti-SLA/LP	Positive	+2	Not reported in SLE without concurrent AIH; high discriminatory value if present
IgG (maximum 2 points)
IgG	> ULN	+1	Hypergammaglobulinaemia is common in SLE (approximately 50%); not discriminatory
IgG	> 1.1 × ULN	+2	IgG > 2 × ULN is associated with cirrhosis risk in SLE-AIH overlap (OR: 11.0; 95%CI: 1.42-85.2) and may serve as a red flag, but is not specific to AIH
Liver histology (maximum 2 points)
Histology	Compatible with AIH	+1	Lupus hepatitis shows non-specific lobular hepatitis that may score +1 despite absence of true AIH; biopsy with C1q immunofluorescence is essential
Histology	Typical of AIH	+2	Interface hepatitis with portal plasma cells is typical of AIH; high discriminatory value in SLE context
Viral hepatitis excluded (maximum 2 points)
Hepatitis A, B, C negative	Yes	+2	SLE patients are generally seronegative for viral hepatitis → all SLE patients score +2 by default, further inflating the score
Score interpretation and SLE-specific problems
≥ 7: Definite AIH			In SLE: ANA (+2) + elevated IgG (+2) + viral hepatitis excluded (+2) = 6 points before histology is assessed; minimal histological abnormality tips to ‘definite AIH’ falsely
6: Probable AIH			In Swedish SLE cohort, 13.9% met ‘probable AIH’ serologically; biopsy-confirmed AIH was only 2.8% - over-diagnosis by > 5-fold

Per American Association for the Study of Liver Diseases 2019 and European Association for the Study of the Liver 2025 guidelines, neither the revised nor the simplified International Autoimmune Hepatitis Group scoring systems should be used for diagnosing overlap syndromes. In systemic lupus erythematosus, antinuclear antibody and hypergammaglobulinaemia inflate the score independently of hepatic autoimmune hepatitis activity, leading to systematic over-diagnosis. In a Swedish systemic lupus erythematosus cohort, 13.9% met ‘probable autoimmune hepatitis’ serologically, while biopsy-confirmed autoimmune hepatitis was only 2.8%. Liver biopsy with C1q immunofluorescence remains mandatory for definitive diagnosis. SLE: Systemic lupus erythematosus; ANA: Antinuclear antibody; SMA: Smooth muscle antibody; LKM1: Liver kidney microsomal antibody type 1; AIH: Autoimmune hepatitis; SLA: Soluble liver antigen; LP: Liver-pancreas; IgG: Immunoglobulin G; ULN: Upper limit of normal; OR: Odds ratio; CI: Confidence interval.