Autoimmune hepatitis overlap syndrome: Clinical presentation, treatment response, and disease evolution: Tertiary centre experience

Background: Autoimmune hepatitis (AIH) overlap syndromes are conditions wherein features of AIH coexist with those of primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC). We aimed to evaluate their clinical presentation, treatment response, and disease outcome in an Arab cohort. Methods: AIH overlap patients, based on the Paris criteria for PBC/AIH overlap (n = 19), and revised International Autoimmune Hepatitis Group (IAIHG) score for PSC/AIH overlap (n = 17) were reviewed at a single center in Saudi Arabia, from 2001 to 2024. Biopsy-proven standalone AIH patients (n = 93) were included as controls. The primary endpoint was disease progression, liver transplantation, or mortality. Results: Overall, the AIH and overlap syndrome cohorts were diagnosed at similar ages. Post-treatment Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores did not improve in the PBC/AIH cohort (P > 0.05), while in PSC/AIH, the CTP (P = 0.005) and Mayo Clinic scores improved (P = 0.002). In PBC/AIH and PSC/AIH cohorts, disease progression and disease remission rates were comparable. The median relapse-free survival (RFS) was 10.4 years for PBC/AIH, and 13.8 years for PSC/AIH cohorts (P = 0.256). The 5- and 10-year RFS rates for the AIH, PBC/AIH, and PSC/AIH cohorts were 92.3% and 72.7%, 81.3% and 53.4%, and 81.4% and 67.9%, respectively. Higher initial Mayo (P = 0.035) and CTP score (P = 0.028) predicted development of disease composite endpoint (disease progression, liver transplantation, or death). Conclusion: Despite lack of standardized treatment protocols, AIH, and overlap syndromes respond comparably well to treatment, in addition to similar disease remission and RFS between PBC/AIH and PSC/AIH patients. More extended follow-up studies are warranted for patients with overlap syndrome.