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1. Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Author

Evangelos Bakaros, Ioanna Voulgaridi, Vassiliki Paliatsa, Nikolaos Gatselis, Georgios Germanidis, Evangelia Asvestopoulou, Stamatia Alexiou, Elli Botsfari, Vasiliki Lygoura, Olga Tsachouridou, Iordanis Mimtsoudis, Maria Tseroni, Styliani Sarrou, Varvara A. Mouchtouri, Katerina Dadouli, Fani Kalala, Simeon Metallidis, George Dalekos, Christos Hadjichristodoulou, and Matthaios Speletas

Subjects
COVID-19, IL18, TLR2, TLR4, CD14, CD40, Microbiology, QR1-502
Abstract

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211, and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe, and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data support the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708, and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

Published
2023
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2. Histological activity despite normal ALT and IgG serum levels in patients with autoimmune hepatitis and cirrhosis

Author

Alena Laschtowitz, Kalliopi Zachou, Vasiliki Lygoura, Simon Pape, Finn Derben, Elmar Jaeckel, Sergio Oller-Moreno, Sören Weidemann, Till Krech, Felix Piecha, Gerhard Schön, Anna-Maria Liebhoff, Munira Al Tarrah, Michael Heneghan, Joost P.H. Drenth, George Dalekos, Richard Taubert, Ansgar Wilhelm Lohse, and Christoph Schramm

Subjects
Autoimmune hepatitis, Biochemical remission, Histological activity, Liver biopsy, Cirrhosis, mHAI, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: In autoimmune hepatitis (AIH), normal levels of transaminases and IgG define biochemical remission and are considered the best surrogate markers for histological remission. This study assessed whether this also applies to patients with AIH cirrhosis. Methods: In this European multicentric study, we included 125 biopsies from 113 patients with AIH and histologically proven cirrhosis; 105 biopsies from 104 patients with AIH without cirrhosis served as controls. Biochemical parameters were available within 4 weeks of biopsy. AIH activity was graded according to the modified Hepatitis Activity Index (mHAI), with mHAI ≥4/18 considered to indicate risk of disease progression. Results: In total, 47 out of 125 liver biopsies were obtained from patients with AIH cirrhosis and normal ALT levels at time of biopsy. Only 26% (12/47) of those livers showed histological remission (mHAI

Published
2021
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3. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

Author

Christophe Corpechot, Fabrice Carrat, Farid Gaouar, Frederic Chau, Gideon Hirschfield, Aliya Gulamhusein, Aldo J. Montano-Loza, Ellina Lytvyak, Christoph Schramm, Albert Pares, Ignasi Olivas, John E. Eaton, Karim T. Osman, George Dalekos, Nikolaos Gatselis, Frederik Nevens, Nora Cazzagon, Alessandra Zago, Francesco Paolo Russo, Nadir Abbas, Palak Trivedi, Douglas Thorburn, Francesca Saffioti, Laszlo Barkai, Davide Roccarina, Vicenza Calvaruso, Anna Fichera, Adèle Delamarre, Esli Medina-Morales, Alan Bonder, Vilas Patwardhan, Cristina Rigamonti, Marco Carbone, Pietro Invernizzi, Laura Cristoferi, Adriaan van der Meer, Rozanne de Veer, Ehud Zigmond, Eyal Yehezkel, Andreas E. Kremer, Ansgar Deibel, Jérôme Dumortier, Tony Bruns, Karsten Große, Georges-Philippe Pageaux, Aaron Wetten, Jessica Dyson, David Jones, Olivier Chazouillères, Bettina Hansen, Victor de Lédinghen, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolao, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Dougla, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vincenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vila, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, and Gastroenterology & Hepatology

Subjects
Liver Cirrhosis, FibroScan, Mortality, PBC, Prognosis, Transplantation, Hepatology, Prognosi, Liver Cirrhosis, Biliary, Liver Cirrhosi, Vibration, Follow-Up Studie, Cohort Studies, Liver, Elasticity Imaging Technique, Retrospective Studie, Humans, Elasticity Imaging Techniques, Cohort Studie, Retrospective Studies, Follow-Up Studies, Human
Abstract

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p

Published
2022

4. Towards Personalized Immunotherapy in Sepsis: The PROVIDE Randomized Clinical Trial

Author

Konstantinos Leventogiannis, Evdoxia Kyriazopoulou, Nikolaos Antonakos, Antigone Kotsaki, Iraklis Tsangaris, Dimitra Markopoulou, Inge Grondman, Nikoletta Rovina, Vassiliki Theodorou, Eleni Antoniadou, Ioannis Koutsodimitropoulos, George Dalekos, Glykeria Vlachogianni, Karolina Akinosoglou, Vassileios Koulouras, Apostolos Komnos, Theano Kontopoulou, Athanassios Prekates, Antonia Koutsoukou, Jos W.M. van der Meer, George Dimopoulos, Miltiades Kyprianou, Mihai G. Netea, and Evangelos Giamarellos-Bourboulis

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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5. Early suPAR-Guided Anakinra Treatment in COVID-19 Pneumonia: Subgroup Analyses and 90-Day Outcomes of the SAVE-MORE Trial

Author

Karolina Akinosoglou, Antigone Kotsaki, Ioanna-Maria Gounaridi, Eirini Christaki, Simeon Metallidis, Georgios Adamis, Archontoula Fragkou, Massimo Fantoni, Aggeliki Rapti, Ioannis Kalomenidis, Georgios Chrysos, Gloria Boni, Ilias Kainis, Zoi Alexiou, Francesco Castelli, Francesco Saverio Serino, Petros Bakakos, Emanuele Nicastri, Vassiliki Tzavara, Asimina Safarika, Sofia Ioannou, Lorenzo Dagna, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Matteo Bassetti, Vasileios Kotsis, Andrea Angheben, George Tsoukalas, Carlo Selmi, Olga-Maria Spiropoulou, Michael Samarkos, Michael Doumas, Georgia Damoraki, Aikaterini Masgala, Ilias Papanikolaou, Aikaterini Argyraki, Marcantonio Negri, Konstantinos Leventogiannis, Styliani Symbardi, Nikolaos K. Gatselis, Vasileios Petrakis, Mihai G. Netea, Periklis Panagopoulos, Vissaria Sakka, Haralampos Milionis, George Dalekos, and Evangelos Giamarellos-Bourboulis

Published
2022
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6. Predictors of HBsAg loss after cessation of nucleo (s)tide analogue therapy in asian patients with low HBsAg levels

Author

Milan Sonneveld, SM Chiu, Jun Yong Park, Apichat Kaewdech, Wai-Kay Seto, Yasuhito Tanaka, Ivana Carey, Margarita Papatheodoridi, Florian van Bömmel, Sylvia Brakenhoff, Thomas Berg, Fabien Zoulim, Sang Hoon Ahn, George Dalekos, Nicole Erler, Christoph Hoener zu Siederdissen, Heiner Wedemeyer, Markus Cornberg, Man-Fung Yuen, Kosh Agarwal, Andre Boonstra, Maria Buti, T Piratvisuth, George Papatheodoridis, Chien-Hung Chen, and Benjamin Maasoumy

Subjects
Hepatology
Published
2022
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8. Two-year safety and efficacy of tenofovir alafenamide in chronic hepatitis B: a HEllenic multicenter ReAl-life CLInical Study (HERACLIS-TAF)

Author

George Papatheodoridis, Konstantinos Mimidis, Spilios Manolakopoulos, Nikolaos Gatselis, Ioannis Goulis, Andreas Kapatais, Emmanouil Manesis, Themistoklis Vasileiadis, Christos Triantos, Demetrious N. Samonakis, Vasilis Sevastianos, Stylianos Karapatanis, Ioannis Elefsiniotis, Melanie Deutsch, Theodora Mylopoulou, Margarita Papatheodoridi, Hariklia Kranidioti, Polyxeni Agorastou, Theofanie Karaoulani, Anastasia Kyriazidou, Konstanitnos Zisimopoulos, and George Dalekos

Subjects
Hepatology
Published
2022
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9. Hepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicentre cohort study

Author

Margarita Papatheodoridi, Tung‐Hung Su, Emilia Hadziyannis, Chun‐Hsun Liao, Αfroditi Orfanidou, Hung‐Chi Yang, Kalliopi Zachou, Chun‐Jen Liu, Anastasia Kourikou, Nikolaos Gatselis, Spilios Manolakopoulos, George Dalekos, Jia‐Horng Kao, Stephanos Hadziyannis, and George V. Papatheodoridis

Subjects
Cohort Studies, Hepatitis B virus, Carcinoma, Hepatocellular, Hepatitis B, Chronic, Hepatology, Withholding Treatment, Liver Neoplasms, Humans, Hepatitis B e Antigens, Neoplasm Recurrence, Local, Antiviral Agents
Abstract

Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs.This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102). Propensity score (PS) 1:1 matching was applied to adjust for patients' origin, age and sex.During a median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5-year cumulative HCC incidence of 5.1% and 4.9% respectively (log-rank, P = .836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P = .510) or Asian origin (1.3% vs 2.2%; log-rank, P = .873). In both cases and controls, HCC incidence was independently associated with age and PAGE-B score. In cases alone, HCC development after NA discontinuation was associated only with pretreatment platelet counts and PAGE-B score, but not with any type of relapse or HBsAg loss.Our findings suggest that discontinuation of effective long-term NA therapy in non-cirrhotic CHBe- patients are not associated with increased HCC risk, which is not affected by post-NA relapses and/or HBsAg loss.

Published
2021

10. 521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

Author

Simone A Thair, Yudong He, Yehudit Hasin-Brumshtein, Suraj Sakaram, Rushika R Pandya, Jiaying Toh, David C Rawling, Melissa Remmel, Sabrina Coyle, George Dalekos, Ioannis Koutsodimitropoulos, Glykeria Vlachogianni, Eleni Gkeka, Eleni Karakike, Georgia Damoraki, Nikolaos Antonakos, Medical Degree, Purvesh Khatri, Evangelos J Giamarellos, and Timothy Sweeney

Subjects
Innate immune system, business.industry, medicine.medical_treatment, CD14, Lymphocyte differentiation, Gene signature, Virus, Transcriptome, AcademicSubjects/MED00290, Cytokine, Immune system, Infectious Diseases, Oncology, Poster Abstracts, Immunology, medicine, business
Abstract

Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

Published
2020
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11. Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

Author

George V. Papatheodoridis, George Dalekos, Ramazan Idilman, Vana Sypsa, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Margarita Papatheodoridi, Nikolaos Gatselis, Rhea Veelken, Marta Lopez-Gomez, BE (Bettina) Hansen, Savvoula Savvidou, Anastasia Kourikou, John Vlachogiannakos, Kostas Galanis, Cihan Yurdaydin, Rafael Esteban, Harry Janssen, Thomas Berg, Pietro Lampertico, George V. Papatheodoridis, George Dalekos, Ramazan Idilman, Vana Sypsa, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Margarita Papatheodoridi, Nikolaos Gatselis, Rhea Veelken, Marta Lopez-Gomez, BE (Bettina) Hansen, Savvoula Savvidou, Anastasia Kourikou, John Vlachogiannakos, Kostas Galanis, Cihan Yurdaydin, Rafael Esteban, Harry Janssen, Thomas Berg, and Pietro Lampertico

Abstract

Background & Aims: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were a

Published
2021
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13. Low HBcrAg and HBsAg levels identify patients most likely to achieve sustained response after nucleos(t)ide analogue cessation: results from a global individual patient data meta-analysis (create study)

Author

Milan Sonneveld, Jun Yong Park, Wai-Kay Seto, Yasuhito Tanaka, Ivana Carey, Margarita Papatheodoridi, Fabien Zoulim, Sang Hoon Ahn, George Dalekos, Christoph Hoener zu Siederdissen, Markus Cornberg, Man-Fung Yuen, Kosh Agarwal, Andre Boonstra, Maria Buti, George Papatheodoridis, and Benjamin Maasoumy

Subjects
Hepatology
Published
2020
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14. Real-world experience from tenofovir alafenamide use in chronic hepatitis B: an Hellenic multicenter real-life clinical study (HERACLIS-TAF)

Author

George Papatheodoridis, Konstantinos Mimidis, Spilios Manolakopoulos, Nikolaos Gatselis, Ioannis Goulis, ANDREAS Kapatais, Emmanouil Manesis, Themistoklis Vasileiadis, Christos Triantos, Demetrious N. Samonakis, Vasilis Sevastianos, Stylianos Karapatanis, Ioannis Elefsiniotis, Melanie Deutsch, Theodora Mylopoulou, Margarita Papatheodoridi, Hariklia Kranidioti, Polyxeni Agorastou, Theofanie Karaoulani, Anastasia Kyriazidou, Konstanitnos Zisimopoulos, and George Dalekos

Subjects
Hepatology
Published
2020
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15. Antimitochondrial antibodies in patients with autoimmune hepatitis: a large multicenter study

Author

Nikolaos Gatselis, Kalliopi Zachou, Aldo Montano-Loza, Eduardo Luiz Rachid Cançado, Teruko Arinaga-Hino, Paolo Muratori, Cumali Efe, Annarosa Floreani, Pietro Invernizzi, Atsushi Takahashi, Akinobu Takaki, Benedetta Terziroli Beretta-Piccoli, Bart Van Hoek, Ellina Lytvyak, Laura Vilar Guedes, Tuğrul Purnak, Nora Cazzagon, Vasiliki Lygoura, Pinelopi Arvaniti, Eirini Rigopoulou, Luigi Muratori, and George Dalekos

Subjects
Hepatology
Published
2020
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16. Prediction of elastographic reversion of cirrhosis after 5 years of entecavir or tenofovir disoproxil fumarate therapy in caucasian chronic hepatitis B patients

Author

Papatheodoridis, George Dalekos, George Yurdaydin, Cihan and Sypsa, Vana van Bommel, Florian Buti, Maria Calleja Panero, Jose Luis Chi, Heng Goulis, Ioannis Manolakopoulos, Spilios and Loglio, Alessandro Voulgaris, Theodoros Gatselis, Nikolaos and Keskin, Onur Veelken, Rhea Lopez-Gomez, Marta Hansen, Bettina Savvidou, Savvoula Kourikou, Anastasia and Vlachogiannakos, Ioannis Galanis, Kostas Idilman, Ramazan and Esteban, Rafael Janssen, Harry Berg, Thomas Lampertico, Pietro

Published
2019

17. Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis delta

Author

Gökhan, Kabaçam, Heiner, Wedemeyer, Berna, Savaş, Onur, Keskin, George, Dalekos, Fehmi, Tabak, Ramazan, Idilman, Andreas, Erhardt, Kendal, Yalçın, Mithat A, Bozdayi, Hakan, Bozkaya, Michael, Manns, Hans, Dienes, Cihan, Yurdaydın, E K, v Wagner, 0-Belirlenecek, TR169081, TR172516, TR155837, and TR11968

Subjects
Adult, Male, Quantitative Surface Antigen, HBsAg, HBcAg, Hepatitis D, Chronic, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Statistics, Nonparametric, Medicine, Humans, Aged, Hepatitis B virus, Hepatitis delta Antigens, Hepatitis B Surface Antigens, Hepatology, biology, business.industry, Age Factors, virus diseases, Alanine Transaminase, gamma-Glutamyltransferase, Hepatitis B, Middle Aged, Delta Antigen, medicine.disease, Hepatitis D, Hepatitis B Core Antigens, Immunohistochemistry, digestive system diseases, HBeAg, Alanine transaminase, Liver, Chronic Delta Hepatitis, Immunology, biology.protein, Female, business, Biomarkers
Abstract

Background & Aims Immunohistochemical assessment of liver tissue in chronic delta hepatitis (CDH) is underinvestigated. Aim of the study was (i) to assess variables associated with hepatitis D antigen (HDAg), hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) staining in the liver. Methods Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HBsAg, HBcAg and HDAg immunohistochemical (IHC) staining was semiquantitatively assessed. Results Hepatitis D antigen immunohistochemical staining displayed positive correlations with age and alanine aminotransferase (ALT) and negative correlations with serum HBsAg (P = 0.01 for all). HBsAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology (P

Published
2014
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18. Monitoring and comorbidities in patients with chronic hepatitis B currently treated with nucleos(t)ide analogs.

Author

Siakavellas S, Goulis J, Manolakopoulos S, Triantos C, Gatselis N, Tsentemidou E, Kranidioti H, Ζisimopoulos Κ, Τsoulas C, Dalekos G, and Papatheodoridis G

Abstract

Background: Long-term monotherapy with nucleos(t)ide analogs (NAs) represents the treatment option for the majority of patients with chronic hepatitis B (CHB), an aging population with a greater likelihood of comorbidities. We assessed the prevalence of concurrent non-hepatic diseases and the safety monitoring in a large cohort of CHB patients receiving NAs and their potential impact on disease outcomes., Methods: We included 500 consecutive CHB patients from 5 major tertiary Greek centers, under long-term therapy with an NA. Epidemiological/clinical characteristics and data on concomitant disease, drug use and investigations ordered were collected., Results: The mean age was 58 years and 66% were male. Most patients were receiving tenofovir disoproxil fumarate (TDF, 60%) or entecavir (ETV, 37%) monotherapy. Decompensated cirrhosis at baseline was present in 10%, while hepatocellular carcinoma (HCC) under therapy developed in 21 patients. The median duration of total NA therapy was 56 and of latest therapy 42 months. The most common (prevalence >10%) comorbidities were hypertension (28%), non-HCC cancer(s) (12%), and diabetes (11%). Patients with a longer duration of latest therapy (≥4 vs. <4 years) were older (mean age: 58 vs. 56 years, P=0.004), had more frequent history of prior use of NA(s) (53% vs. 35%, P<0.001), and less frequent liver decompensation (5% vs. 13%, P=0.008) and non-HCC cancers (8% vs. 15%, P=0.020). HCC developed more frequently in patients with than in those without diabetes (11% vs. 3%, P=0.022)., Conclusion: Greek CHB patients currently treated with NAs, almost exclusively ETV or TDF, are often older than 60 years, have several comorbidities, and thus require careful management., Competing Interests: Conflict of Interest: This study was supported by an unrestricted grant from Gilead Sciences Hellas, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Published
2021
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19. Type 1 autoimmune hepatitis presenting with severe autoimmune neutropenia.

Author

Doumtsis P, Oikonomou T, Goulis I, Zachou K, Dalekos G, and Cholongitas E

Abstract

Autoimmune hepatitis (AIH) is a progressive, chronic liver disease characterized by unresolving hepatocellular inflammation of autoimmune origin. The clinical spectrum may vary from asymptomatic presentation, to non-specific symptoms such as fatigue, arthralgias, nausea and abdominal pain, to acute severe liver disease. AIH is characterized by the presence of interface hepatitis and portal plasma cell infiltration on histological examination, hypergammaglobulinemia, and positive autoantibodies. AIH is associated with other autoimmune diseases and its course is often accompanied by various non-specific hematological disorders. However, the coexistence of autoimmune neutropenia (AIN) is infrequent. We present a case of a female patient diagnosed with type 1 AIH and agranulocytosis on presentation. A diagnosis of AIN was established, based on the patient's sex, the underlying liver disease, the absence of alternative causes, the presence of atypical anti-neutrophil cytoplasmic antibodies in patient's serum and the favorable and dose-dependent treatment of both pathologic entities with corticosteroids and mycophenolate mofetil., Competing Interests: Conflict of Interest: None

Published
2018
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