In addition, Exon3 was overexpressed to clarify the effective site of Numb gene for comparison. AAV.Numb can alleviate CLF and suppressed the activation of Notch signaling and the differentiation of hepatic progenitor cells (HPCs) into biliary epithelial cells (BECs), and the anti-CLF effect of Numb-Exon3 was similar to that of full-length Numb. The findings revealed that Numb gene may be a new therapeutic target for PBC and that Exon3 may be an effective site. The gene discussed is NUMB; the disease is primary biliary cholangitis.