No Evidence of Bacterial Biofilm in Recurrent Cholangitis in Primary Sclerosing Cholangitis: A Case Presentation and Introduction of a Hypothesis

Abstract

Inflammation and fibrosis of the bile ducts are the defining pathological characteristics of Primary Sclerosing Cholangitis (PSC). Among patients listed for liver transplantation, one fifth experience two or more episodes of cholangitis. A previously unexplored explanation for the recurrent nature of cholangitis in PSC is bacterial colonization of the biliary epithelium in the form of biofilm that confers resistance to antibiotics and hosts' phagocytic machinery. The primary aim of the current case was to assess whether bacteria could be seen on the liver explant and whether they organized in the form of biofilm.Figure 1A 60-year-old male with Crohn's disease and PSC presented with recurrent bacterial cholangitis. He did not have dominant bile duct strictures on cholangiogram. Despite ERCP maneuvers, internal-external biliary duct drain placement and long term rotating antibiotics, he continued to experience culturepositive polymicrobial cholangitis and sepsis. During liver transplantation, purulent material was oozing from the liver. Detailed examination of the explant liver pathology using standard light microscopy with gram stain, however, did not reveal any bacterial organism or features of biofilm. We did observe classic features of PSC (images). The patient is well one year after transplant. The pathophysiology of recurrent bacterial cholangitis in a subpopulation of PSC patients is unknown. How enteric organisms gain entry into bile is unclear. The unique association of PSC with inflammatory bowel disease makes portal vein one potential route as bacteria translocate across an inflamed gastrointestinal tract. The presence of dominant strictures of the bile ducts is another logical etiologic suspect in recurrent cholangitis. While several studies have shown that antibiotics improve liver biochemistry in PSC patients, no study has specifically investigated whether patients with or without bacterial cholangitis respond differently to treatment. In our case, despite intraoperative pus, we did not observe bacteria or biofilm on the explant. It may be because the explant specimen was extensively fixed in formalin, known to affect the mucus layer of the mucosa where adherent bacteria reside. Future studies should examine biliary microbiome using fresh unprocessed liver tissue and bile. If biofilm exists in PSC patients with recurrent cholangitis, biofilm-specific treatments such as rifampin, aspirin and hydrophobic bile salts could be further investigated.Figure 2Figure 3