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Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Background Until recently, transplantation from hepatitis C–positive donors was relatively contraindicated as eradication of active hepatitis C previously required an interferon-based regimen that has been associated with rejection in solid organ transplantation. New interferon-free treatment regimens for hepatitis C have fewer adverse events and higher cure rates than interferon-based regimens. Interferon-free regimens have been shown to be safe in the liver transplantation literature, but little is known about the safety and efficacy of treatment in heart transplantation. Case Description and Discussion Here we report a case of successful eradication of hepatitis C with a non–interferon-based regimen using ledipasvir-sofosbuvir following combined orthotopic heart and liver transplantation. Based on the prevalence of hepatitis C in the general population, inclusion of hepatitis C–positive donors for heart transplantation can expand this component of the donor pool 3- to 6-fold. Conclusions In carefully selected patients and recipients, inclusion of hepatitis C–positive donors may allow for expansion of the donor pool.

Role of donor specific antibodies (DSAs) in liver allograft function has not been fully defined. We report an ABO compatible orthotopic liver transplant case with DSAs to donor HLA, where the patient developed immediate antibody-mediated rejection (AMR).The patient, a 43-year-old female with cirrhosis, underwent ABO-compatible living-donor liver transplant from her husband. On post-operative day (POD)1, serum transaminases were sharply elevated. Retrospective testing of pre-transplant serum demonstrated presence of strong class I and class II anti-HLA antibodies and positive T- and B-cell flow-cytometric crossmatches (FCXM). Transaminase levels improved with plasmapheresis and thymoglobulin. On POD7, her liver enzymes became elevated again and allograft biopsy stained positive for C4d. Patient was treated with intravenous immunoglobulin and rituximab and recovered over time. Pre-transplant sera of patient were retrospectively tested by C1q assay to determine the cytotoxic function of DSAs; DSAs were positive for C1q binding. Our results suggest that pre-liver transplant antibody testing may be helpful in identifying patients at risk for development of AMR.

Background Chronic infection with hepatitis E virus (HEV) has recently been recognized in immunocompromised or immunosuppressed individuals. Case Report We report a case of concurrent HEV and human herpes virus-6 (HHV-6) infection, documented by serum HEV RNA and HHV-6 DNA, in an orthotopic liver transplant (OLT) recipient in the United States, where HEV genotype 3 infection, although prevalent, is considered to be self-limited and almost always asymptomatic. The coinfection was accompanied by elevated serum aminotransaminases, liver biopsies demonstrating chronic hepatitis, and the presence of HEV RNA in the tissue. After lowering of immunosuppressive therapy and 2 courses of valganciclovir, sequential clearance of the viruses and normalization of the serum aminotransaminases were observed. Conclusions HEV infection can lead to chronic hepatitis in OLT recipients, and evaluation of this virus should be considered in immunosuppressed individuals with unexplained liver test abnormalities.

P0646 LOWER RISK OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS TREATED WITH ENTECAVIR: A REACH-B ANALYSIS OF THE ENUMERATE STUDY J. Ahn, M. Nguyen, H. Lee, J. Lim, C. Pan, H. Te, T. Tran, H.N. Trinh, D. Lau, D. Chu, A. Min, T.-S. Leduc, A. Pillai, H. Bae, S. Do, A. Mannalithara, A.S. Lok, W.R. Kim, on behalf of the ENUMERATE Investigators and Asian Health Foundation. Oregon Health & Science University, Portland, Stanford University, Stanford, Tufts University, Boston, Yale University, New Haven, NYU Langone, New York City, University of Chicago, Chicago, Cedars Sinai, Los Angeles, San Jose Gastroenterology, San Jose, Beth Israel Medical Center, Boston, Albert Einstein College of Medicine, Mount Sinai Beth Israel, New York City, Leduc Medical Group Inc, Fountain Valley, Emory University, Atlanta, St. Vincent Medical Center, Los Angeles, Digestive Health Associates of Texas, Plano, University of Michigan, Ann Arbor, United States E-mail: ahnj@ohsu.edu

Background: Immunization for Hepatitis A (HAV) and Hepatitis B (HBV) is recommended for Hepatitis C (HCV) patients as superinfection can increase the risk of adverse events. Since immunogenicity increases with each successive dose in the vaccine series, completing the series provides the best chance of maximal protection. Standard of care (SOC) approaches such as provider driven vaccination after serologic testing results in poor series completion rates. Universal vaccination (UV), where patients are vaccinated for HAV/HBV without prior serologic testing, is a commonly identified as an effective vaccination strategy. Patient and provider outreach interventions have also been recommended to improve vaccination rates. Studies of the effectiveness and implementation of these strategies is lacking. Methods: Veteran patients were eligible if they attended a HCV group medical appointment and had evidence of chronic HCV without history of immunization/serologic evidence of immunity to HBV alone or HAV and HBV. Using a 2x2 factorial design assuming no interactions, consenting subjects were randomized to one of four vaccination strategies: 1) UV alone 2) UV plus outreach 3) outreach plus SOC 4) or SOC alone. UV was initiated at enrollment prior to serologic testing. Outreach interventions included a phone and mailed reminder to subjects about the need for vaccination and an electronic reminder sent to subjects' primary care provider. Vaccine series completion rates were compared amongst the two strategies using a chi-square analysis. A series completion failure was defined as failure to receive all three doses of the HBV or combined HAV/HBV series within 14 months of study enrollment. The implementation of each strategy was studied including recording the time per subject required to perform each strategy. Results: Those who received the UV strategy had a reduction in series completion failures compared to SOC RR: 0.46 (0.27; 0.81); p < 0.01. The mean time needed to conduct UV was 7.3 (± 3) minutes. Unnecessary vaccinations based upon follow up serologies were observed. Those receiving UV were more likely to receive an unnecessary vaccination RR: 4.4 (1.7; 12). Subjects receiving the outreach intervention did not experience a reduction in series completion failures compared to SOC RR: 0.82 (0.49; 1.67); p=0.3. The mean time needed to perform outreach interventions was 7.75 (± 2) minutes. Conclusions: The UV strategy resulted in a large reduction of series completion failures compared to SOC, with time required similar to the outreach strategy. Outreach efforts were labor intensive and did not result in lower rates of series completion failures. Further study of clinic workflow is needed to reduce the time required to perform UV and to identify methods to avoid unnecessary vaccinations.

Methods: Sixty-five patients with cirrhosis tested for ETP with/without TM. Clinical, endoscopic variables, presence/absence of PVT by Doppler-US and/or TC examination were collected at basal evaluation and up to 4 years. The incidence of de novo PVT was the primary clinical end-point. We also considered transplantation freesurvival. ETP-ratio upper than the 95° percentile of 173 healthycontrols defined TM-resistance. Results: ETP-ratio was not different by comparing patients with (n =1 2) vs without PVT (n = 53) at basal evaluation. Among no-PVT patients, 11 developed de novo PVT in the follow-up. The incidence of PVT was higher in those patients with TM-resistance (n = 36) also after adjustment for Child-score (HR:7.68; 90%-CI: 1.32–44.54, p = 0.017). Seventeen patients experienced at least one PHT-related complication and 23 patients died or were transplanted. The mean survival time-free of transplantation was 2.7 vs 3.6 years by comparing, respectively, patients with vs without TM-resistance (p = 0.005, log-rank test). However, only Child-score independently predicted transplantation free-survival. Conclusions: The occurrence of PVT should be explained, in part, by the pro-coagulant imbalance described in patients with advanced liver disease. TM-resistance could be a potential modifiable factor to improve survival in patients with cirrhosis. P465 SVR IS ASSOCIATED WITH NO RISK REDUCTION OF HCC DEVELOPMENT IN PATIENTS WITH HCV-RELATED CIRRHOSIS. A PROSPECTIVE, UP-TO 23 YEARS, COHORT FOLLOW-UP STUDY S. Bruno 1

Pathological comparison of radiofrequency and microwave ablation in combination with transarterial chemoembolization in the treatment of hepatocellular carcinoma R. Vasnani, M. Ginsburg, T. Doshi, A. Kozlov, J. Hart, H. Te, T. VanHa; Radiology, University of Chicago, Chicago, IL; University of Florida College of Medicine, Gainesville, FL; Pathology, University of Chicago, Chicago, IL; Medicine, University of Chicago, Chicago, IL

Aim Presence of anti-donor HLA antibodues is a contraindication to transplantation in most solid organs. In contrast, most patients with high titer donor specific antibodies (DSA) and positive flow cytometric crossmatch (FCXM) still undergo liver transplantation. Antibody mediated rejection (AMR) may or may not develop after liver transplantation in such patients. We speculated that despite positive crossmatch results, cytotoxic function of existing and/or de novo DSA is what will ultimately predict development of AMR. Methods In this study we report two conflicting cases of liver transplant patients with high titer pre-transplant DSA and positive FCXM. Pre-transplant sera of patient A and B were retrospectively tested with a C1q assay to determine the cytotoxic function of DSAs. Results One patient (patient A) developed hyperacute AMR shortly after transplantation while the second patient (patient B) did not develop any signs of AMR and her post-transplant period was uneventful. In patient A, shortly after transplantation, serum amino transaminase and bilirubin levels became elevated. Serum HLA antibody testing showed high levels of class I and class II DSAs that resulted in positive T and B cell FCXM. Positive C4d staining of liver allograft biopsy indicated an episode of AMR. Patient was treated with plasmapheresis (days 1-9), Rituximab and IVIG (days 9-13) and Thymoglobulin (days 2-8). Levels of DSA and positive FCXM decreased overtime and 4 years post-transplant DSA antibodies were no longer present. In contrast, patient B did not develop any signs of post-transplant complications related to presence of HLA antibodies. Consistent with our hypothesis at the time of transplant, DSA of patient A were positive for C1q factor. In contrast C1q was negative on DSA of patient B. Conclusions We conclude that pre-transplant antibody testing and C1q assay should be considered as pre-transplant tests to be performed to liver transplant patients. Larger studies should be performed to confirm our findings.

169 DIFFERENT PATTERN OF DECOMPENSATION IN ALCOHOLIC VERSUS NON-ALCOHOLIC LIVER CIRRHOSIS M. Kuehne, J. Wiegand, P. Pradat, J. Moessner, F. Zoulim, C. Trepo, H.L. Tillmann. Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany; Department of Hepatogastroenterology, Hotel Dieu Hospital University, Lyon, France; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA E-mail: johannes.wiegand@medizin.uni-leipzig.de

Background and Aim: Cardiac dysfunction in cirrhosis is a problem of the ‘blind side of the heart’. Without firm diagnostic criteria, the exact prevalence of cirrhotic cardiomyopathy remains unknown. We evaluate left ventricle (LV) standard echocardiographic (Echokg) and colour Doppler myocardial imaging (DMI) pattern of cirrhotic patients (pts) with the aim to assess correlation with Child–Pugh score. Patients and Methods: 58 of pts (27 males, 31 females, age 53.6±11.6 years) with liver cirrhosis of various etiology and 21 healthy controls (14 males, 7 females, age 49.0±12.0 years) were studied. Cirrhosis stage was evaluated by Child–Pugh scoring. All subjects had undergone 2D and colour DMI. Results: No clear differences between standard Echokg parameters depicting LV systole and diastole were noticed. Slight increase of LV and left atrium size was observed in the cirrhotic pts as compared with controls (Fisher exact test: p = 0.0489 and p = 0.0015, respectively). Also weak correlation of EF and E, A waves with cirrhosis score was found (Spearman correlation: CEF = 0.32109, p = 0.0039; CE = 0.22771, p = 0.0436; CA = 0.41774, p = 0.0001). Meanwhile cirrhotic pts had markedly decreased septal and mean Ea which further deteriorated depending on cirrhosis score (Spearman correlation: CEa mean= −0.78686, p< 0.0001; CEa septal= −0.78176, p< 0.0001). Filling pressure (E/Ea) was upgraded in the cirrhotic pts (Spearman correlation: CE/Ea= 0.65457, p< 0.0001), that was more pronounced in the Child– Pugh C group (controls vs C: 0.084 vs 0.17). Longitudinal systolic function estimated by mean strain (S) and strain rate (SR) was decreased in the cirrhotic pts compared with controls (Spearman correlation: CS = −0.54209, p< 0.0001; CSRS = −0.46828, p< 0.0001). S and SR were positively correlated with diastolic septal and mean mitral anular Ea (Pearson correlation: CS and Ea septal = 0.493, p< 0.0001; CS and Ea mean = 0.451, p< 0.0001; CSR and Ea septal = 0.540, p< 0.0001; CSR and Ea mean = 0.508, p< 0.0001). Conclusions: DMI indices might be a useful tool in predicting cardiac dysfunction in cirrhotic patients. Following parameters mean and septal annulus Ea, filling pressure E/Ea and mean longitudinal strain and strain rate may therefore represent the best available screening test to diagnose the cirrhotic cardiomyopathy syndrome.