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2. Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within milan criteria

Author

Parisi, Ioanna, Tsochatzis, Emmanuel, Wijewantha, Hasitha, Rodríguez-Perálvarez, Manuel, Luca, Laura De, Manousou, Pinelopi, Fatourou, Evangelia, Pieri, Giulia, Papastergiou, Vassilios, Davies, Neil, Yu, Dominic, Luong, TuVinh, Dhillon, Amar Paul, Thorburn, Douglas, Patch, David, OʼBeirne, James, Meyer, Tim, and Burroughs, Andrew K.

Published
2014
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3. Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease

Author

Buzzetti, Elena, primary, Hall, Andrew, additional, Ekstedt, Mattias, additional, Manuguerra, Roberta, additional, Guerrero Misas, Marta, additional, Covelli, Claudia, additional, Leandro, Gioacchino, additional, Luong, TuVinh, additional, Kechagias, Stergios, additional, Manesis, Emanuel K., additional, Pinzani, Massimo, additional, Dhillon, Amar P., additional, and Tsochatzis, Emmanuel A., additional

Published
2019
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4. Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease

Author

Buzzetti, Elena, Hall, Andrew, Ekstedt, Mattias, Manuguerra, Roberta, Misas, Marta Guerrero, Covelli, Claudia, Leandro, Gioacchino, Luong, TuVinh, Kechagias, Stergios, Manesis, Emanuel K., Pinzani, Massimo, Dhillon, Amar P., Tsochatzis, Emmanuel A., Buzzetti, Elena, Hall, Andrew, Ekstedt, Mattias, Manuguerra, Roberta, Misas, Marta Guerrero, Covelli, Claudia, Leandro, Gioacchino, Luong, TuVinh, Kechagias, Stergios, Manesis, Emanuel K., Pinzani, Massimo, Dhillon, Amar P., and Tsochatzis, Emmanuel A.

Abstract

Background Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. Aim To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and x4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Results Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. Conclusions CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials., Funding Agencies|European Association for the Study of the Liver; AIGO (Associazione Italiana Gastroenterologi Ospedalieri); M.I.M.I. (Montecatini Interactive Medicine International)

Published
2019
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5. IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection

Author

Pallett, Laura J., Davies, Jessica, Colbeck, Emily J., Robertson, Francis, Hansi, Navjyot, Easom, Nicholas J.W., Burton, Alice R., Stegmann, Kerstin A., Schurich, Anna, Swadling, Leo, Gill, Upkar S., Male, Victoria, Luong, TuVinh, Gander, Amir, Davidson, Brian R., Kennedy, Patrick T.F., Maini, Mala K., and Wellcome Trust

Subjects
Hepatitis B virus, T-Lymphocytes, Programmed Cell Death 1 Receptor, Immunology, Receptors, Antigen, T-Cell, CD8-Positive T-Lymphocytes, Granzymes, Hepatitis B, Chronic, Antigens, CD, Transforming Growth Factor beta, Humans, Antigens, Research Articles, 11 Medical and Health Sciences, Cell Proliferation, Receptors, CXCR6, Interleukin-15, Brief Definitive Report, Models, Immunological, Autocrine Communication, Phenotype, Liver, Interleukin-2, Receptors, Virus, Receptors, Chemokine, Immunologic Memory
Abstract

Pallett et al. identify tissue-resident memory CD8 T cells compartmentalized in the healthy human liver that expand in controlled hepatotropic infection and can swiftly produce antiviral cytokines. This prototype may inform the development of liver-targeted T cell immunotherapy., The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)–infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-betloEomesloBlimp-1hiHobitlo T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69+CD103+ CXCR6+CXCR3+). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance.

Published
2017

6. The workload and impact of a dedicated cancer of unknown primary (CUP) service on patients with imaging suggestive of metastatic disease

Author

Mclaren, Alistair, primary, Ulahannan, Danny, additional, Keen, Emily, additional, Stewart, Grant, additional, Bell, James, additional, Planche, Katie, additional, Power, Niall, additional, Navalkissoor, Shaunak, additional, Craig, Rachel, additional, Luong, TuVinh, additional, Watkins, Jennifer, additional, Clark, Ian, additional, and Gillmore, Roopinder, additional

Published
2017
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7. IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection

Author

Pallett, Laura J., primary, Davies, Jessica, additional, Colbeck, Emily J., additional, Robertson, Francis, additional, Hansi, Navjyot, additional, Easom, Nicholas J.W., additional, Burton, Alice R., additional, Stegmann, Kerstin A., additional, Schurich, Anna, additional, Swadling, Leo, additional, Gill, Upkar S., additional, Male, Victoria, additional, Luong, TuVinh, additional, Gander, Amir, additional, Davidson, Brian R., additional, Kennedy, Patrick T.F., additional, and Maini, Mala K., additional

Published
2017
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8. Progressive epigenetic dysregulation in neuroendocrine tumour liver metastases

Author

Karpathakis, Anna, primary, Dibra, Harpreet, additional, Pipinikas, Christodoulos, additional, Feber, Andrew, additional, Morris, Tiffany, additional, Francis, Joshua, additional, Oukrif, Dahmane, additional, Mandair, Dalvinder, additional, Pericleous, Marinos, additional, Mohmaduvesh, Mullan, additional, Serra, Stefano, additional, Ogunbiyi, Olagunju, additional, Novelli, Marco, additional, Luong, TuVinh, additional, Asa, Sylvia L, additional, Kulke, Matthew, additional, Toumpanakis, Christos, additional, Meyer, Tim, additional, Caplin, Martyn, additional, Beck, Stephan, additional, and Thirlwell, Christina, additional

Published
2017
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9. Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor

Author

Karpathakis, Anna, primary, Dibra, Harpreet, additional, Pipinikas, Chistodoulos, additional, Feber, Andrew, additional, Morris, Tiffany, additional, Francis, Joshua, additional, Oukrif, Dahmane, additional, Mandair, Dalvinder, additional, Pericleous, Marinos, additional, Mohmaduvesh, Mullan, additional, Serra, Stefano, additional, Ogunbiyi, Olagunju, additional, Novelli, Marco, additional, Luong, TuVinh, additional, Asa, Sylvia L., additional, Kulke, Matthew, additional, Toumpanakis, Christos, additional, Meyer, Tim, additional, Caplin, Martyn, additional, Meyerson, Matthew, additional, Beck, Stephan, additional, and Thirlwell, Christina, additional

Published
2016
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11. IL-2 high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection.

Author

Pallett LJ, Davies J, Colbeck EJ, Robertson F, Hansi N, Easom NJW, Burton AR, Stegmann KA, Schurich A, Swadling L, Gill US, Male V, Luong T, Gander A, Davidson BR, Kennedy PTF, and Maini MK

Subjects
Antigens immunology, Antigens, CD metabolism, Autocrine Communication drug effects, CD8-Positive T-Lymphocytes drug effects, Cell Proliferation drug effects, Granzymes metabolism, Hepatitis B virus drug effects, Hepatitis B, Chronic immunology, Hepatitis B, Chronic pathology, Hepatitis B, Chronic virology, Humans, Immunologic Memory drug effects, Interleukin-15 pharmacology, Liver drug effects, Liver pathology, Phenotype, Programmed Cell Death 1 Receptor metabolism, Receptors, Antigen, T-Cell metabolism, Receptors, CXCR6, Receptors, Chemokine metabolism, Receptors, Virus metabolism, Transforming Growth Factor beta pharmacology, CD8-Positive T-Lymphocytes immunology, Interleukin-2 metabolism, Liver immunology, Liver virology
Abstract

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet lo Eomes lo Blimp-1 hi Hobit lo T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69 + CD103 + CXCR6 + CXCR3 + ). These tissue-resident memory T cells (T RM ) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted T RM , including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 T RM to survive while exerting local noncytolytic hepatic immunosurveillance., (© 2017 Pallett et al.)

Published
2017
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