Th109 - The Peripheral Immunological Profile Determines the Clinical Presentation and Prognosis of Patients with Autoimmune Hepatitis

Lourdes Ruíz-Ortega – Liver Unit – Hospital Universitario Vall d’Hebrón; Paula Esteban – Liver Unit – Hospital Universitario Vall d’Hebrón; Mª Teresa Sanz-Martínez – Immunology Department – Hospital Universitario Vall d’Hebrón; Laura Viñas-Gimenez – Immunology Department – Hospital Universitario Vall d’Hebrón; Cesar Gaspari – Immunology Department – Hospital Universitario Vall d’Hebrón; Juan-Carlos Ruíz-Cobo – Liver Unit – Hospital Universitario Vall d’Hebrón; Ignacio Vaz-Romero – Liver Unit – Hospital Universitario Vall d’Hebrón; Adriana Palom – Liver Unit – 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD); María Buti – Liver Unit – Hospital Universitario Vall d’Hebrón; Mar Riveiro-Barciela – Liver Unit – Hospital Universitario Vall d’Hebrón

Abstract Text: Autoimmune hepatitis (AIH) is associated with T cells dysregulation. We aimed to assess how lymphocyte phenotype (LP) at diagnosis varies with patient characteristics and if it can predict the response to immunosuppression.

A prospective study from 2020-2023 included all new histologically-proven AIH diagnoses. Before of immunosuppression, an extended peripheral LP was conducted, correlating with baseline characteristics and subsequent clinical events. All patients received a uniform therapy régimen of corticosteroids (CS) (20-60mg) and azathioprine (1-2mg/Kg), excluding variant forms of AIH.

Thirty-four patients were included: 70.6% women, 58 years (IQR47-73), 26(70.6%) debuted as acute hepatitis (AST/ALT>10-fold normality), 31(91.2%) presented any antibody with ANAs≥1/80 (82.4%) and xANCA (31.3%) as the most frequent. Eight (23.5%) subjects had cirrhosis.

At diagnosis, cirrhotic patients showed a trend toward increased CD8+TEMRA presence (51.6vs36.1,p=0.079). Acute hepatitis cases had a higher proportion of pre-switch-memory CD27+BL(7.1vs3.0,p=0.003), naïve-CD4+(45.8vs20.7,p=0.015), CD3+(73.8vs69.3,p=0.025), CD8+(23.6vs17.7,p=0.043), and lower CD4+Effector+Central memory phenotype (52.4vs73.6,p=0.045).
After a median follow-up of 25 months, complete biochemical response (CBR) was achieved in 23(64.7%) patients being higher among those presenting as acute hepatitis compared with those with non-acute presentation (76.9%vs 25%, p=0.013), but similar regardless of cirrhosis presence (50%vs69.2%,p=0.279).
CBR was associated with baseline higher values of leukocytes, platelets, AST, bilirubin, CD4+ naïve(47.3vs27.0,p=0.008), CD8+ naïve (26.1vs9.5,p < 0.001), and lower IgG levels (1622vs2350 IU/mL,p=0.010), CD4+ effector memory (20.4vs35.5,p=0.024) and CD4 Effector+Central memory (52.0vs65.0,p=0.059).

Conclusion: A dominant effector CD4+ and CD8+ phenotype predicts incomplete biochemical response (CBR) in AIH patients. Evaluating effector T cells at diagnosis may enable early detection of challenging cases, facilitating timely intervention.