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253. 1416 PLASMA PHOSHOLIPID PROFILING BY METABONOMICS: HIGHLY ACCURATE OUTCOME PREDICTION IN DECOMPENSATED CIRRHOSIS

Author

McPhail, M.J.W., primary, Shawcross, D., additional, Lewis, M., additional, Coltart, I., additional, Abeles, R.D., additional, Taylor, N., additional, O'Grady, J., additional, Heaton, N., additional, Auzinger, G., additional, Bernal, W., additional, Want, E., additional, Holmes, E., additional, Wendon, J., additional, and Taylor-Robinson, S., additional

Published
2012
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254. 283 MIXED-PHENOTYPE HEPATOCELLULAR CARCINOMA IN LIVER TRANSPLANTS AFTER USE OF TRANSARTERIAL CHEMOEMBOLIZATION (TACE) IS ASSOCIATED WITH ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) SIGNALLING PATHWAY

Author

Iansante, V., primary, Zen, Y., additional, Barbarulo, A., additional, Starling, C., additional, Chokshi, S., additional, Heaton, N., additional, Williams, R., additional, Bubici, C., additional, Quaglia, A., additional, and Papa, S., additional

Published
2012
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258. Improving the Diagnostic Criteria for Primary Liver Graft Nonfunction in Adults Utilizing Standard and Transportable Laboratory Parameters: An Outcome‐Based Analysis

Author

Al‐Freah, M. A. B., McPhail, M. J. W., Dionigi, E., Foxton, M. R., Auzinger, G., Rela, M., Wendon, J. A., O'Grady, J. G., Heneghan, M. A., Heaton, N. D., and Bernal, W.

Abstract

Current diagnostic criteria for primary nonfunction (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single‐center study was conducted of all adults (n = 1286) who underwent primary liver transplant (LT) 2000–2008 in our center. Laboratory variables during the first post LTweek were analyzed. Forty‐two patients (3.7%) had 2‐week graft failure. Transplant albumin, day‐1 aspartate aminotransferase (AST), day‐1 lactate, day‐3 bilirubin, day‐3 international normalized ratio (INR), and day‐7 ASTwere independently associated with PNFon multivariate logistic regression. PNFscore =(0.000280*D1AST)+ (0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D3 INR)+(0.00153*D7 AST)‐(0.0972*TxAlbumin)‐4.5503. Receiver operating curve analysis showed the model area under receiver operating curve (AUROC) of 0.912 (0.889–0.932) was superior to the current United Kingdom (UK) PNFcriteria of 0.669 (0.634–0.704, p < 0.0001). When applied to a validation cohort (n = 386, 34.4% patients), the model had AUROCof 0.831 (0.789–0.867) compared to the UKearly graft dysfunction criteria of 0.674 (0.624–0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post‐LTdays only (AUROCof 0.818, 0.776–0.856, p = 0.001). This model is superior to the current UK PNFcriteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and nonmarginal). A large single‐center study redefining primary nonfunction following liver transplantation develops and validates a novel method to predict death or graft failure in the first two weeks following transplantation. See the editorial from Sung on page 1158.

Published
2017
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260. P77 A Pharmacist delivered stratified conversion protocol from Hepatitis B Immunoglobulin (HBIG) to tenofovir or entecavir is efficacious, safe and cost-effective for prevention of recurrence of Hepatitis B virus (HBV) in Liver Transplant (LT) recipients

Author

Knighton, S., primary, Agarwal, K., additional, Heneghan, M., additional, O'Grady, J., additional, Bruce, M., additional, Carey, I., additional, Heaton, N., additional, and Suddle, A., additional

Published
2011
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261. P95 Molecular mechanisms of monocyte reprogramming in acute liver failure: importance of hepatically derived anti-inflammatory mediators

Author

Antoniades, C. G., primary, Zingarelli, V., additional, Possamai, L., additional, Mistry, R., additional, Abeles, R. D., additional, Bruce, M., additional, McPhail, M. J. W., additional, Heaton, N., additional, Auzinger, G., additional, Bernal, W., additional, Vergani, D., additional, Thursz, M. R., additional, and Wendon, J. A., additional

Published
2011
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266. 910 EXPANSION OF HEPATIC MACROPHAGES IN ACETAMINOPHEN-INDUCED ACUTE LIVER FAILURE: WHERE DO THEY COME FROM AND WHAT IS THEIR ROLE?

Author

Antoniades, C.G., primary, Quaglia, A., additional, Mitry, R., additional, Bruce, M., additional, Hussain, M., additional, McPhail, M., additional, Al-Hussaini, H., additional, Bernal, W., additional, Auzinger, G., additional, Taams, L., additional, Heaton, N., additional, Thursz, M., additional, Vergani, D., additional, and Wendon, J., additional

Published
2011
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269. LONG TERM OUTCOME OF EX SITU RIGHT LOBE SPLIT GRAFTS IN LIVER TRANSPLANTATION

Author

Valente, R., primary, Dar, F., additional, Cherian, T., additional, Jassem, W., additional, OʼGrady, J., additional, Agarwal, K., additional, Aluvihare, V., additional, Heneghan, M., additional, Suddle, A., additional, Melendez, Vilca H., additional, Prachalias, A., additional, Srinivasan, P., additional, Rela, M., additional, and Heaton, N., additional

Published
2010
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278. PWE-046 Factors that influence outcome of patients with severe upper gastrointestinal variceal bleeding. A single centre experience

Author

Al-Freah, M A, primary, Gera, A, additional, Martini, S, additional, Shawcross, D, additional, Abeles, R D, additional, Taylor, N, additional, Auzinger, G, additional, Harrison, P, additional, Devlin, J, additional, Heneghan, M A, additional, Heaton, N D, additional, Bernal, W, additional, and Wendon, J A, additional

Published
2010
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281. Late cellular rejection in paediatric liver transplantation: Aetiology and outcome

Author

D'Antiga, L, Dhawan, A, Portmann, B, Francavilla, R, Rela, M, Heaton, N, Mieli-Vergani, G, D'Antiga, L, Dhawan, A, Portmann, B, Francavilla, R, Rela, M, Heaton, N, and Mieli-Vergani, G

Abstract

Background. Acute cellular rejection, though mostly encountered during the first 3 months after liver transplant, may occur later on. Clinical features and outcome of children experiencing late cellular rejection (LCR) have not been described to date. Patients and Methods. A total of 20 children who developed acute rejection 6 months or more after liver transplant were studied for history of early rejection, levels of immunosuppression, causes of low immunosuppression, viral infections, signs of autoimmunity, and HLA mismatch. All liver biopsies were reviewed. Fifteen patients with no history of LCR were randomly selected as controls. Results. Of 20 children 5 were appropriately immunosuppressed, although 15 were not. Causes of low immunosuppression were: unknown (seven), poor compliance (three), posttransplant lymphoproliferative disease, (two), hepatocellular carcinoma recurrence (one), tuberculosis (one), gastroenteritis (one). Of 20 patients early rejection occurred in 13 and cytomegalovirus infection in 5. At last follow-up 10 children have persistent graft dysfunction, of whom 5 have progressed to de novo autoimmune hepatitis, 2 to chronic rejection, one has persistent graft dysfunction with recurrent cytomegalovirus activation, one has hepatic artery thrombosis and one is likely to have persistent poor compliance. None of the 15 controls developed de novo autoimmune hepatitis or any other form of persistent graft dysfunction at the time of last follow-up. Conclusion. Late cellular rejection in children is usually due to low or decreased immunosuppression and is associated with long-term complications. Prompt intervention to correct inadequate immunosuppression and careful follow-up of the other patients to identify other treatable conditions is essential.

Published
2002

282. Bone mineral density and height gain in children with chronic cholestatic liver disease undergoing transplantation

Author

D'Antiga, L, Moniz, C, Buxton-Thomas, M, Cheeseman, P, Gray, B, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, Dhawan, A, Baker, AJ, Heaton, ND, D'Antiga, L, Moniz, C, Buxton-Thomas, M, Cheeseman, P, Gray, B, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, Dhawan, A, Baker, AJ, and Heaton, ND

Abstract

Background. Osteodystrophy is a well-described complication of chronic liver disease. Previous reports in adults and children undergoing liver transplantation (LT) were discordant, with the former showing no improvement of bone disease in the first year after transplantation and the latter demonstrating remarkable benefit from it. Our aim was to perform a pilot study on osteodystrophy in children undergoing LT and evaluate the contribution of growth on bone mineral density (BMD) changes. Methods. We studied six patients (two male), with a median age at transplantation of 8.8 (range 3.8-16.6) years. Indications for transplantation were biliary atresia and progressive familial intrahepatic cholestasis (three patients each). BMD was studied with dual-energy x-ray absorptiometry and biochemical markers of liver and bone function in patients before and at 3, 6, and 12 months after LT. Results. Median L2-L4 spinal BMD was 0.54 g/cm2 (range 0.29-0.87) before LT, and 0.58 g/cm2 (0.27-0.86) at 3 months, 0.66 g/cm2 (0.36-1.00) at 6 months, and 0.76 g/cm2 (0.44-1.02) at 12 months after LT (P=0.005). Median height was 133 (range 93-167) cm before LT, and 134 (93-167) at 3 months, 136 (97-167) at 6 months, and 139 (102-167) at 12 months after LT. There was direct correlation between height gain and total body BMD improvement (r=0.929, P=0.007). Conclusion. BMD in children with chronic cholestatic liver disease improves remarkably by 12 months after LT. Catch-up growth in children can account for the different effect of LT on bone density between adult and pediatric populations in the first year after surgery.

Published
2002

283. Reply

Author

Howard, E R and Heaton, N

Subjects
Letters to the Editor
Published
1993

288. Histological features during graft dysfunction in paediatric liver transplantation

Author

D'Antiga, L, Dhawan, A, Khan, S, Cheeseman, P, Rela, M, Heaton, N, Mieli-Vergani, G, Portmann, B, D'Antiga L, Dhawan A, Khan S, Cheeseman P, Rela M, Heaton ND, Mieli-Vergani G, Portmann B, D'Antiga, L, Dhawan, A, Khan, S, Cheeseman, P, Rela, M, Heaton, N, Mieli-Vergani, G, Portmann, B, D'Antiga L, Dhawan A, Khan S, Cheeseman P, Rela M, Heaton ND, Mieli-Vergani G, and Portmann B

Published
2000

289. The effect of liver transplantation (LT) on hepatic osteodystrophy in children

Author

D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, Mieli-Vergani G, D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, and Mieli-Vergani G

Published
2000

291. Outcomes for Adults with Type 1 Diabetes Referred with Severe Hypoglycaemia and/or Referred for Islet Transplantation to a Specialist Hypoglycaemia Service.

Author

Byrne, M. L., Hopkins, D., Littlejohn, W., Beckford, R., Srinivasan, P., Heaton, N., Amiel, S. A., and Choudhary, P.

Subjects
ISLANDS of Langerhans transplantation, TREATMENT of diabetes, TYPE 1 diabetes, HYPOGLYCEMIA treatment, PHYSIOLOGICAL effects of glucose, INSULIN pumps
Abstract

Islet transplantation alone (ITA) is indicated for patients with type 1 diabetes (T1D) with disabling severe hypoglycaemia (SH) despite optimised medical therapy. We examined outcomes for patients referred to an islet transplant unit with recurrent SH. Retrospective case note audit of 45 patients with ≥ 1 SH per year who were referred to our ITA unit between 2009–2012; 36 patients attended follow-up appointments. The cohort was 52.8 % male, mean (± SD) age 43.9 (± 11.4) years, and duration of diabetes 26.5 (± 12.9) years. Baseline HbA1c was 8.3 % (± 1.7) (67.2 mmol/mol), median (IQR) frequency of SH was 6.0 (2.0–24.0) per/patient/year and 83.3 % had impaired awareness of hypoglycaemia (IAH). 80.6 % of patients were referred from other secondary diabetes services, 22.2 % had completed structured education, and 30.6 % were using continuous subcutaneous insulin infusion (CSII). Seventeen patients were optimised with conventional therapy; SH reduced from 2.0 (1.5–9.0) to 0.0 (0.0–0.5) episodes/patient/year; p < 0.001, and there was concurrent improvement in HbA1c (8.1–7.7 %; 65.0 vs. 60.7 mmol/mol; p = 0.072). Ten patients were listed for transplantation as they were not optimised despite structured education, CSII, and continuous glucose monitoring (CGM). The remaining 9 had a reduction in SH [7.0 (4.8–40.5) to 4.0 (2.5–6.3) episodes/patient/ year; p = 0.058] and either left the service (n = 5) or are still being optimised (n = 4). In conclusion, 47.2 % of patients presenting with problematic hypoglycaemia resolved with optimal medical therapy, with a further 25 % achieving clinically relevant improvement, however 27.8 % required transplantation despite access to all therapies. Provision of expertise in hypoglycaemia management is essential to focus limited transplant resources on those who need it most. [ABSTRACT FROM AUTHOR]

Published
2015
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292. Modification of Human Islet Preparation: An Effective Approach to Improve Graft Outcome After Islet Transplantation?

Author

Zhao, M., Choudhary, P., Srinivasan, P., Tang, H., Heaton, N., Fung, M., Barthel, A., Bornstein, S. R., Amiel, S. A., and Huang, G. C.

Subjects
ISLANDS of Langerhans transplantation, REVASCULARIZATION (Surgery), ENDOTHELIAL cells, TYPE 1 diabetes, TREATMENT of diabetes, PATIENTS
Abstract

Revascularisation of transplanted islets is an essential prerequisite for graft survival and function. However, current islet isolation procedures deprive the islets of endothelial tubulets. This may have a detrimental effect on the revascularisation process of islets following transplantation. We hypothesise that modification of the isolation procedure that preserves islet endothelial vessels may improve the islet revascularisation process following transplantation. Here, we present a modified islet isolation method by which a substantial amount of endothelial cells still attached to the islets could be preserved. The islets with preserved endothelial cells isolated by this method were revascularised within 3 days, not observed in islets isolated by standard methods. Further, we observed that grafts of islets isolated by standard methods had more patches of dead tissue than islet grafts obtained by the modified method, indicating that attached endothelial cells may play an important role in the islet revascularisation process and potentially help to improve the transplantation outcome. [ABSTRACT FROM AUTHOR]

Published
2015
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293. Biochemical markers of bone metabolism and bone mineral density (BMD) in children before and after liver transplantation

Author

D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, Mieli-Vergani G, D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, and Mieli-Vergani G

Published
1999

294. OUTCOME OF HEPATOPULMONARY SYNDROME IN CHILDREN

Author

Al-Hussaini, Abdulrahman, primary, Samyn, M., additional, Bansal, S., additional, Heaton, N., additional, Rela, M., additional, Buxton-Thomas, M., additional, Mieli-Vergani, G., additional, and Dhawan, A., additional

Published
2006
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