453Association of Clostridium difficile Infection (CDI) with Excess Mortality after Liver Transplantation (LT) for Hilar Cholangiocarcinoma (CCA)

Abstract

Background: LT patients are at higher risk of CDI compared to other hospitalized patients. Since LT patients with CCA often require antibacterial therapy for various infections, they may be at increased risk of CDI. However, the epidemiology, risk factors and impact of CDI in LT recipients with CCA have not been studied. Objectives: We describe the epidemiology and risk factors for CDI and assess its impact on patient outcomes among LT patients with CCA. Methods: We conducted a retrospective cohort study of patients who underwent neoadjuvant chemo-radiotherapy followed by LT for CCA during 20042013 at a single tertiary referral center. Results: The population consisted of 124 patients who were followed for median duration of 4.2 years (interquartile range (IQR) 1.5-6.7 years). 15.9% developed CDI within 9.3 years post-transplant (19 episodes in 15 patients).10 (67%) were male. Thirteen (68%) were community-onset CDI. Initial treatment regimen consisted of oral metronidazole in 11 (58%) and oral vancomycin in 8 (42%) episodes. 4 patients developed recurrent CDI. Recurrent CDI was treated with oral metronidazole (50%) and oral vancomycin (50%). No patient died from CDI and none developed toxic megacolon or required surgical intervention. On univariable analysis, LT patients with history of a pre-transplant infection (within 6 months pretransplant) had lower risk of post-transplant CDI (HR 0.3 (0.1-0.9); P=0.04). Post-transplant CDI was associated with higher mortality when adjusted for recurrent CCA (HR 4.6 (1.4-15.2); P=0.01). Conclusion: CDI is a common infectious complication after LT for CCA, and is associated with a higher risk of mortality. Its prevention, through antimicrobial stewardship, may improve the outcomes of LT patients with CCA.  A single-center, retrospective cohort study of adult patients who underwent liver transplantation for biopsy proven hilar CCA at the Mayo Clinic Rochester between 2004 and 2012.  Patients’ demographic and clinical data was extracted from the electronic medical records.  All patient records were reviewed from six months prior to liver transplantation until the last date of follow up.  Descriptive statistical analysis was performed. Background Hilar cholangiocarcinoma (CCA) is an aggressive cancer and is the second most common primary hepatobiliary cancer. The annual incidence of CCA in the USA is rising and is currently estimated at 1.2/100,000 in the United States. Many patients present with unresectable, locally advanced disease at the time of diagnosis. Early experiences with liver transplantation for CCA were disappointing due to high tumor recurrence rates and poor patient survival. However, the Mayo Clinic, in 1993, developed a protocol using neoadjuvant chemoradiation and staging abdominal exploration before liver transplantation for selected patients and this has shown encouraging results. Mayo Clinic has the largest cohort of patients with CCA who have undergone liver transplantation. CCA has re-emerged as an indication for liver transplantation. However, data regarding the epidemiology of Clostridium difficile infections in this specific patient cohort and their impact on patient and graft survival are non-existent. We believe that patients with CCA who undergo liver transplantation have unique characteristics that make them more vulnerable to infections when compared with other liver transplant recipients. These include background disease (Primary sclerosing cholangitis), protocol effects, higher rates of living donor liver transplantation and Roux en Y anastomosis. Aims:  To describe the epidemiology of Clostridium difficile infections in LT recipients with biopsy proven CCA.  To assess the risk factors for Clostridium difficile infections in LT recipients with biopsy proven CCA.  To assess the impact of Clostridium difficile infections on patient and allograft survival in LT recipients with biopsy proven CCA. Objectives