A novel non-transecting ligation technique for clinically mimetic cholestatic cirrhosis in rats

The conventional common bile duct ligation (CBDL) model suffers from high postoperative mortality (frequently exceeding 50%), which severely limits longitudinal monitoring of disease progression and complications such as hepatopulmonary syndrome (HPS). We developed an improved CBDL (MCBDL) to preserve the continuity of bile duct, and compared MCBDL (n=40) with traditional CBDL (n=40) and sham operation (n=10) within 42 days. MCBDL captures cirrhosis and extrahepatic organ injury while significantly improving survival (72.5% vs. 45%, P=0.003) and attenuating systemic inflammation (IL-6: 117 ± 11 vs. 153 ± 26 pg/mL, P=0.047). Scanning electron microscopy revealed persistent secretory activity in ligated epithelia of both groups, but only CBDL permitted leakage from isolated stumps, creating a pathogenic cycle driving mortality. By preserving ductal continuity, MCBDL is associated with significantly reduced mortality while maintaining the hallmark features of cholestatic cirrhosis (METAVIR F4) and HPS-related extrahepatic complications, providing a stable platform for mechanistic studies.