Table 1.

Nonclassical Phenotypes of Autoimmune Hepatitis at Presentation

Nonclassical phenotype	Features	Implications
Acute onset	Frequency, 25%–75%63,65 Newly developed or exacerbated pre-existent disease61,63	Can resemble acute viral, drug-induced, toxic or ischemic injury61 Responds well to standard treatment61,63
Acute severe (fulminant) onset	Frequency, 3%–6%66,67 Onset encephalopathy ≤26 weeks61 Classical features may be absent68 Centrilobular necrosis in 86%67 Lymphoplasmacytic infiltrates and interface hepatitis in 50%–90%67 Heterogeneous hypoattenuated regions by unenhanced CT71	Can resemble acute viral, drug-induced, toxic or ischemic injury61 Requires transplantation evaluation61 Variable response to corticosteroids and possible complications (sepsis)61
Asymptomatic presentation	Frequency, 25%–34%72,73 Histological features similar to symptomatic patients73 Become symptomatic in 26%–70%72,73 Survival without treatment possible72	Low frequency of resolution if untreated (12% vs 63%)74 Lower 10-year survival if untreated than in treated severe AIH (67% vs 98%)74 Consider treating all patients74
Autoantibody-negative phenotype	Scoring systems diagnostic, 19%–22%75 Acute liver failure possible83,84 Anti-SLA positive in 9%–31%26,83	Steroid-responsive, 67%–87%75,81 Test for nonstandard antibodies75 Exclude celiac disease89,90,93
Atypical histological patterns	Centrilobular necrosis in 29%94 Bile duct injury or loss possible100,101	May reflect severity and acuity of AIH94 or suggest other diagnoses102
Graft dysfunction posttransplant	Recurrent AIH, 8%–12% after 1st year122 De novo AIH, 1%–9% within 9 years113 Anti-GSTT1 common in de novo AIH128	Variable steroid response113 Cirrhosis and graft failure possible113 Retransplantation required, 23%–50%113
Overlap syndrome	Mixed features of AIH+PBC or PSC102,107 “Paris criteria” for AIH+PBC105,135	Variable treatment response52,53 Frequently treated with steroids+UDCA130

CT, computed tomography; AIH, autoimmune hepatitis; anti-SLA, antibodies to soluble liver antigen; anti-GSTT1, antibodies to glutathione-S-transferase T1; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; UDCA, ursodeoxycholic acid.