BACKGROUND AND AIMS: Histological diagnosis of autoimmune pancreatitis (AIP) may be difficult to obtain preoperatively. Based on promising results using new-generation "end-cutting" needles, we aimed to assess the utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in enhancing diagnostic levels of International Consensus Diagnostic Criteria (ICDC) in probable AIP patients and in defining the specific AIP subtype. METHODS: Adult patients with suspected AIP were prospectively and competitively enrolled at four Centers. Definitive AIP diagnosis, according to ICDC, or patients recently treated with steroids were excluded. A 22-gauge end-cutting needle was used in all cases. The primary outcome was the rate of enhanced ICDC levels. Secondary outcomes were rates of level 1 or 2, EUS-FNB diagnostic accuracy, rate of malignancy, and safety. RESULTS: Fifty focal and two diffuse suspected AIP were enrolled (75% male, mean age 57.9±17.3). Final diagnoses were AIP, chronic pancreatitis, and malignancy in 39 (75%), 6 (11.5%), and 7 (13.5%) patients, respectively. EUS-FNB improved the diagnostic level of AIP in 92.3% (74.3% definitive and 17.9% probable). The rate of histology level 1 compatible with a diagnosis of type 1 and type 2 AIP was 73.1% and 50%, respectively. The rate of histology level 2 was 23.1% and 41.7% in type 1 and type 2, respectively. The overall diagnostic accuracy of EUS-FNB was 94.2% [95% CI 84.1-98.8]. Two mild pancreatitis (3.8%) occurred after EUS-FNB. CONCLUSIONS: EUS-FNB using end-cutting needles enhances ICDC criteria in >
90% of patients, ruling out malignancy in focal presentations and defining the specific subtype of AIP. CLINICALTRIAL: gov number, NCT04397731.