NOTCH2 and progressive familial intrahepatic cholestasis type 3: Consequently, eliminating cccDNA from the host cell nucleus by gene-silencing strategies may contribute to a complete cure for hepatitis B. Moreover, there are other rare diseases related to gene mutations that affect the digestive system, such as the canalicular membrane protein ATP-binding cassette subfamily B member 4 (ABCB4) mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3),60 JAG1 gene or receptor NOTCH2 mutations in Alagille syndrome,61 ATP7B gene mutations in Wilson disease,62 and SERPINA1 gene mutations in Alpha-1 anti-trypsin deficiency.63