Post-ERCP persistent hepatocellular secretory failure: clinical profile, biochemical correlates and implications for management strategies

Objective Persistent hepatocellular secretory failure (PHSF) is a rare condition marked by sustained hyperbilirubinaemia despite successful biliary decompression in patients with biliary obstruction. This study aimed to characterise postendoscopic retrograde cholangiopancreatography (ERCP) PHSF and its clinical course. Methods This multicentre retrospective case series included adults with bilirubin >10 mg/dL persisting at least 1 week after ERCP biliary decompression. Data were collected from collaborating tertiary referral sites from January 2015 to January 2021. Exclusion criteria included chronic liver disease, recent hepatotoxic exposure, hepatic malignancy or liver metastasis. The primary aim was to describe the epidemiological and clinical characteristics of post-ERCP PHSF; secondary aims were to identify clinical and biochemical correlates of the degree of persistent hyperbilirubinaemia. Results Thirty-five patients (mean age 65.2 years) were analysed: 25 with pancreatic head mass/distal obstruction and 10 with choledocholithiasis. Mean bilirubin decreased from 27.3±11.9 mg/dL pre-index ERCP to 21.1±9.3 mg/dL pre-second ERCP (p=0.0003). Pre-index ERCP bilirubin was associated with pre-second ERCP bilirubin (R 2 =0.43, p<0.001). Alkaline phosphatase (p=0.0002), platelet count (p=0.04) and time from symptom onset to index ERCP (p<0.001) correlated with pre-second ERCP bilirubin. Patients with self-expanding metal stents (SEMS) had higher pre-second ERCP bilirubin than those with DC (25.4 vs 13.2 mg/dL, p=0.0008). Further intervention during the second ERCP did not significantly reduce the time to halve the bilirubin level (p=0.80). Conclusion Post-ERCP PHSF may persist despite adequate biliary decompression. The findings support careful exclusion of mechanical obstruction while recognising that repeat ERCP intervention may not accelerate bilirubin clearance in patients meeting PHSF criteria. Prospective studies are required to validate diagnostic pathways and evaluate targeted pharmacological therapy.