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sMo1907

Predictive Value of White Blood Cell Differential Count in the Diagnosis ofAcute Cellular Rejection After Liver TransplantationGuo-Ying Wang, Hua Li, Jian Zhang, Qi Zhang, Huan-bing Zhu, Yang Yang, Gui-HuaChen

Background Acute cellular rejection (ACR) after liver transplantation is a significant causeof patient morbidity and can lead to graft loss. Liver biopsy still remains the gold standardfor diagnosis of ACR. Several serum markers for diagnosis of rejection have been reported,but none are simple to measure, low in cost, and high specificity. Some studies haveemphasized the role of eosinophils in ACR. However, the relationship between white bloodcell differential count and ACR still remains unclear. We therefore undertook this study toevaluate the predictive value of white blood cell differential count in the diagnosis of ACRfollowing liver transplantation. Methods Biopsies performed within 2 months followingtransplantation or from patients transplanted for autoimmune diseases were excluded in thestudy because of high doses of steroids. Differential white cell counts were obtained on theday or one day before biopsy. Eosinophil count and its percentage, neutrophil and lymphocytepercentage were evaluated. Eosinophil count ≥ 0.4×10E9/L, eosinophil percentage ≥ 4%,neutrophil percentage≥ 70% and lymphocyte percentage≥ 40% were considered elevated.Sensitivity, specificity, and positive predictive value of eosinophil count and its percentage,neutrophil percentage, and lymphocyte percentage for ACR were determined. Results Thirty-one liver transplant patients, 40 liver biopsies, and differential white blood cell count wereanalyzed. Nineteen biopsies showed ACR (47.6%). The medians of neutrophil percentagein ACR group were significantly lower compared with those in the nonrejection group (p<0.001). Twelve had an elevated neutrophil percentage, including one in ACR group. Anelevated neutrophil percentage excludes ACR with a sensitivity, specificity, and positivepredictive value of 52.4%, 94.7%, and 91.7%, respectively. There was no significant differencein eosinophil count, eosinophil percentage, and lymphocyte percentage between the nonrejec-tion and ACR group (p=0.078, 0.254, and 0.102, respectively). However, in ACR group,there were 7 biopsies (36.8%) with an elevated eosinophil count, eosinophil percentage, orlymphocyte percentage, including 5 with an elevated eosinophil count or its percentage,and 2 with an elevated lymphocyte percentage. No biopsies in the nonrejection group hadan elevated eosinophil count, eosinophil percentage, or lymphocyte percentage. The elevatedthese parameters predicted ACR with a sensitivity of 36.8% but with a specificity of 100%and a positive predictive value of 100%. Conclusions Increased numbers of lymphocytesand eosinophils in peripheral blood are a simple noninvasive diagnostic marker for acuterejection with a specificity of 100%. This simple and cheap test can be used to early predictand diagnose acute cellular rejection following liver transplantation.

Mo1908

The Incidence and Risk Factors of de novo Skin Cancer in the LiverTransplant RecipientsJamak Modaresi Esfeh, Adam Tabba, Ibrahim A. Hanouneh, Deepan S. Dalal, MangeshPagadala, Rocio Lopez, Bijan Eghtesad, Nizar N. Zein

Background: Liver transplantation (LT) increases the risk of de novo malignancies includingskin cancers. However, risk factors for this type of cancers have not been well studied.Objectives: were 1) to assess incidence of skin cancer in LT recipients and 2) to identifythe risk factors associated with greater likelihood for this type of cancer. Methods: Weidentified all adult patients who underwent LT and developed de novo skin cancer post LTat our institution between 1996 and 2009. We excluded the patients with history of skincancer prior to LT. A control group of patients who underwent LT during the same timeperiod and did not develop skin cancer was matched (1:2) for age, gender and geographicalplace of residence. Results: Over a median follow up time of 41.5 (18.0, 98.6) months, 23(2.3%) of 998 patients developed skin cancer post LT. Of whom 10 patients were identifiedwith squamous cell carcinoma, 9 with basal cell carcinoma and 4 with melanoma. Afteradjusting the confounding variables subjects who had combined liver/kidney transplant had22 (95% CI: 5.1, 99) times higher hazard of skin cancer compared to subjects with LTalone. Furthermore patients who had non skin cancer prior to LT had 23 (95% CI: 8.6,60) times higher hazard developing skin cancer after the transplant. Alcohol as the underlyingetiology of liver disease had 4 (95% CI: 1.2, 12.9) times higher hazard of developing skincancer after transplantation. Type or duration of immunosuppression was not associatedwith increased risk of skin cancer post LT. The post-LT survival outcome was not affectedby the development of de novo skin cancer post LT. Conclusions: Skin cancer is relativelycommon in LT recipients and should be monitored particularly in the patients with ahistory of pretransplant malignancy, recipients of combined liver kidney transplant or havingalcoholic cirrhosis as the etiology of underlying liver disease.

S-996AASLD Abstracts

Mo1909

Transient Elastography in Beta Thalassemic Subjects Infected With HCV: anAcceptable Alternative to Liver BiopsyFarhad Zamani, Seyedeh Masoomeh Esalmi, Mohammad R. Ostovaneh, AmirhosseinModabbernia, Fatemeh Sima Saeedian, Reza Malekzadeh, Hossein Poustchi

Background and aim: Transient Elastography(TE) is a recently developed tool for noninvasiveassessment of liver fibrosis, which showed promising results in chronic liver damage. It alsoraises concerns of unreliable measurements due to interference of multiple confoundingfactors including iron overload in thalassemic patients. Studies on validity and reliability ofTE compared to liver biopsy and T2 MRI are scarce. We aimed to evaluate the performanceof TE in assessment of liver fibrosis in beta-thalassemic patients, while taking the effect ofliver iron content( LIC) and other potential confounders into account. Methods: Seventysix HCV positive beta-thalassemic patients who had repeated transfusions underwent TE,biopsy, T2*MRI(within a maximum of three months interval from time of TE) and laboratoryevaluations. The median value of at least ten validated TE score measurements(kPa) wasconsidered representative of the elasticity of the liver. MRI-based LIC was calculated fromT2* MRI results using “CMR tools” software. Biopsy specimens were scored regarding fibrosisstage and inflammation and iron load grade. Relationship of TE scores with other variableswas assessed by Spearman's correlation test and multiple linear regression. Accuracy of TEwas also assessed by ROC curve analysis. Results: Scores of TE increased proportionally toMETAVIR fibrosis stage(r: 0.404 ,P value <0.001), being significantly different for each fibrosisstage(P value <0.001) but independently of MRI based liver iron concentration(r:0.064, Pvalue: 0.581) or liver iron grading in biopsy(r:0.104, P value: 0.376). MRI based LICalso correlated with histologic liver iron grading(r: 0.616, P value<0.001).By multivariateregression analysis, stage of fibrosis (standardized B: 0.22 and 0.42 for stage 3 and 4 offibrosis) along with Gender, inflammation grade, ALT and BMI independently and signific-antly associated with log transformed TE score, but no link found between MRI based LICand TE score(standardized B:0.064, p:0.512). The AUROC for prediction of cirrhosis was0.80 (CI 95%: 0.59-1). A cut-off TE score of 11 had a sensitivity of 77.8% and specificityof 88.1% for diagnosing cirrhosis. Conclusion:TE is a reliable non-invasive tool to evaluateliver fibrosis in HCV infected beta-thalassaemic patients , regardless of LIC. TE also showedacceptable sensitivity and specificity for diagnosis of cirrhosis from other fibrosis stages.

Mo1910

Prevalence of Hepatitis E in New York Among HIV Negative Chronic LiverDisease Population "Is it an Innocent Bystander"Patrick Basu, Thankam Nair, Mikram Jafri, Sakina Farhat, Sajith Foustin, Lynn P. Ang,Kavya Mittimani

Objectives: Hepatitis E is essentially an oro fecal infection with high prevalence in developingcountries. There is limited data available on its prevalence in Urban US. The study evaluatesthe prevalence of Hepatitis E antibody IgG and IgM in New York in patients with chronicliver disease Methods: Four hundred forty (n=440) were divided into 2 groups: group A;control 140 patients without any stigmata of liver disease. Group B, 300 patients with historyof liver disease including hepatitis B 125/300(41%) , Chronic hepatitis C 60/300 (20%),fatty liver 70/300(23%) , Alcoholic liver disease 29/300(10%), HBV HCV co infection 9/300 ( 3%), auto immune hepatitis 2/300(0.6%), PBC /PSC 5/300(2%). HEV antibody IGMand IGG were measured with HEV genotyping. 22/300 (7%) patients were liver transplantrecipients, 6/300 (2%)patients were kidney transplant recipients. 43/300(14%) patients wereIntra venous Drug Abuser.20/300(7%) received Blood products Results: Group (A) HEVIgG positive 13% (18/140), Group B HEV IgG positive 40.6% (122/300) including 3.7%(4/122) having both IgM & IgG positive. The prevalence of HEV IgG was 54% (12/22) inthe liver transplant recipient group and 33% (2/6%) kidney transplant recipient group.Conclusion: The study demonstrates the prevalence of Hepatitis E infection in New Yorkand HEV antibody in CLD. Including transplant donors and recipients. Question remains

the impact and progression of acute or chronic liver disease with concomitant HEV in pre,peri, and post liver transplant recipient. Larger study needs to validateDemographic of patients in Group B

History and genotypic Characteristics

Mo1911

Three-Dimensional Image of Hepatic Hilum by CT Cholangiography WithCarbon Dioxide for Preoperative Assessment of Biliary MalignanciesKojiro Taura, Etsuro Hatano, Takamichi Ishii, Shinji Uemoto

[Background] Curative resection for biliary malignancies involving hepatic hilum is technic-ally-demanding due to complex anatomy of the hepatic hilum. Three-dimensional (3D)presentation of the hepatic hilum structures including bile ducts is supposed to be usefulfor precise understanding of the anatomy and the tumor extension in individual patientsand may improve surgical outcomes. Carbon dioxide (CO2) has been utilized as a radiolucentcontrast material. Because CO2 has opposite radiopacity to iodinated contrast material, it maybe advantageous to CT cholangiography in which 3D images of bile ducts and vasculatures aresimultaneously reconstructed and merged. [Purpose] The purpose of this study is to examineusefulness of CO2 CT cholangiography for preoperative assessment of biliary malignancies.[Patients and Methods] Forty consecutive patients with external biliary drainage (endoscopicnasobiliary drainage (ENBD) or percutaneous transhepatic biliary drainage (PTBD)) whowere considered for surgical resection were the subjects of this study. CO2 was injected viabiliary drainage tubes so that the bile ducts are filled with CO2 (figure 1). The patients werealso given intravenous injection with iodinated contrast media and underwent dynamic CTscan. The arterial and the portal phase images were obtained 5 seconds and 20 secondsafter the peak aortic enhancement time, respectively. 3D images were reconstructed for thearteries and the bile ducts from the arterial phase and for the portal vein from the portalphase with 3D analysis software Virtual Place Lexus (AZE, Japan). [Results] Figure 2 showsa representative case with hilar cholangiocarcinoma involving the right hepatic artery andthe portal vein. Bile ducts were successfully demonstrated in all cases without occurrenceof cholangitis or elevation of liver enzymes. The biliary branches were visualized up to 4.3rd-order branches on the average. The fusion 3D images of the vasculatures and the bileducts were useful for recognition of abnormal anatomy or isolated branches, which are oftenoverlooked in conventional two-dimensional cholangiography. Moreover, the synchronous3D images helped us understand the relative anatomical relationship between the tumorand the surrounding vessels and facilitated precise determination of the cutting line of thebile duct in the operation. Twenty-one patients actually underwent tumor resection andnegative surgical margin was achieved in all but two cases with carcinoma in situ at thecutting line. [Conclusion] 3D CT cholangiography with CO2 is a useful tool for preoperativediagnosis, operative planning, and intraoperative navigation of biliary malignancies involvinghepatic hilum. Sophisticated operations based on the precise understanding of the anatomyand the tumor extension in individual patients are expected to improve surgical outcomes.

S-997 AASLD Abstracts

Figure 1 Axial slice data of CT cholangiography with carbon dioxide

Figure 2 Three-dimensional fusion image of the artery, portal vein, and bile ducts. "T"indicate the tumor.

Mo1912

Changes in Autoimmune Markers Occurring in Liver Transplant RecipientsCarmen M. Stanca, Costica Aloman, Maria Isabel Fiel, Thomas Schiano

Background: Little is known about the pattern of autoimmune markers (AIM) in livertransplantation (LT) recipients, irrespective of the liver disease etiology, in the context ofimmunosuppression. Hepatitis C (HCV) recurrence is universal and some patients developparticularly aggressive disease after LT. We hypothesized that AIM may behave differentlyin LT patients, particularly in those with HCV. Methods: Patients with LT who underwentpost-LT biopsies between Oct 2008 and Aug 2011 were enrolled. Patients had AIM checkedat time of liver biopsy. Demographic data, AIM, liver histology (explant and post-LT biopsies)were analyzed. Non-parametric tests were employed. Data are presented as median (range).Results: Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were includedin the study; 76 patients had AIM at time of LT. Length of follow up since LT was 285(30-1462) days. Sixty percent of patients had HCV at time of LT, 83% developed recurrentHCV. Immunosuppression regimens were similar in these patients. Overall, a significantdecrease in IgA, IgG, IgM, rheumatoid factor and beta-2 microglobulin levels was observedpost LT compared with before LT (p<0.001 for each). HCV patients had higher IgG (p=0.005) and rheumatoid factor (p=0.044) levels before LT compared to non-HCV patients;elevated IgG (p=0.029) and IgM (p=0.045) levels were associated with high HCV grade inthe explant. HCV patients also tended to have increased rheumatoid factor (p=0.071) andbeta-2 microglobulin (p=0.065) levels at time of post LT biopsy. On follow up biopsies,only high IgG levels were associated with increased inflammation as measured by HCVgrade (p=0.012). Smooth muscle antibodies were present at time of LT in higher percentagein patients who will later develop recurrent HCV, although it did not reach statisticalsignificance (p=0.065). Patients who developed recurrent HCV had lower IgG levels at timeof LT as compared to those who did not develop recurrent infection (p=0.004). Some ofthe AIM stayed negative from LT throughout the follow up period (liver cytosol, solubleliver antigen, liver-kidney microsomal). Conclusions: Autoimmune markers change signific-antly after LT, and have a different pattern in HCV patients. Some markers are associatedwith HCV recurrence and advanced inflammation on liver biopsy. Further analysis can helpidentify predictors of severity of HCV recurrence in LT patients.

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