Early-onset versus late-onset nonanastomotic biliary strictures post liver transplantation: risk factors reflect different pathogenesis

Nonanastomotic biliary strictures (NAS) cause significant morbidity post liver transplantation. Timing of stricture development varies considerably, but the relationship between timing of stricture onset and aetiology has not been fully elucidated. Database analysis was performed on all adult patients undergoing liver transplantation between 1st January 1990 and 31st May 2008. Diagnosis of NAS required demonstration on at least two radiological studies. Early NAS were defined as developing <1 year post transplant (minimum 1-year follow-up) and late NAS developing >1 year post transplant (minimum 10-year follow-up). Ninety-six of 397 patients developed NAS (24%); 54 were early-onset NAS (56%) and 42 late-onset NAS (44%). Primary sclerosing cholangitis (PSC) was the only risk factor for NAS overall (P = 0.001). However, when patients with PSC were excluded, older donor age was a significant risk for NAS (P = 0.003). Early-onset NAS were associated with advanced donor age (P = 0.02), high MELD score (P = 0.001) and ABO-identical grafts (P = 0.02), whereas late-onset NAS were associated with PSC (P = 0.0008), bilio-enteric anastomosis (P = 0.006) and tacrolimus (P = 0.0001). Advanced donor age is a significant risk for NAS in patients without PSC. Importantly, aetiology of NAS varies depending on time to stricture development, suggesting early-onset and late-onset NAS may have different pathogenesis.