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151. Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity

Author

Genshaft, Alex S., primary, Subudhi, Sonu, additional, Keo, Arlin, additional, Vasquez, Juan D. Sanchez, additional, Conceição-Neto, Nádia, additional, Mahamed, Deeqa, additional, Boeijen, Lauke L., additional, Alatrakchi, Nadia, additional, Oetheimer, Chris, additional, Vilme, Mike, additional, Drake, Riley, additional, Fleming, Ira, additional, Tran, Nancy, additional, Tzouanas, Constantine, additional, Joseph-Chazan, Jasmin, additional, Villanueva, Martin Arreola, additional, van de Werken, Harmen J. G., additional, van Oord, Gertine W., additional, Groothuismink, Zwier M.A., additional, Beudeker, Boris J., additional, Osmani, Zgjim, additional, Nkongolo, Shirin, additional, Mehrotra, Aman, additional, Feld, Jordan, additional, Chung, Raymond T., additional, de Knegt, Robert J., additional, Janssen, Harry L. A., additional, Aerssens, Jeroen, additional, Bollekens, Jacques, additional, Hacohen, Nir, additional, Lauer, Georg M., additional, Boonstra, Andre, additional, Shalek, Alex K., additional, and Gehring, Adam, additional

Published
2021
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156. The Netherlands Is on Track to Meet the World Health Organization Hepatitis C Elimination Targets by 2030

Author

van Dijk, Marleen, primary, Brakenhoff, Sylvia M., additional, Isfordink, Cas J., additional, Cheng, Wei-Han, additional, Blokzijl, Hans, additional, Boland, Greet, additional, Dofferhoff, Anthonius S. M., additional, van Hoek, Bart, additional, van Nieuwkoop, Cees, additional, Sonneveld, Milan J., additional, van der Valk, Marc, additional, Drenth, Joost P. H., additional, and de Knegt, Robert J., additional

Published
2021
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159. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians

Author

Arends, Pauline, Sonneveld, Milan J, Zoutendijk, Roeland, Carey, Ivana, Brown, Ashley, Fasano, Massimo, Mutimer, David, Deterding, Katja, Reijnders, Jurriën G P, Oo, Ye, Petersen, Jörg, van Bömmel, Florian, de Knegt, Robert J, Santantonio, Teresa, Berg, Thomas, Welzel, Tania M, Wedemeyer, Heiner, Buti, Maria, Pradat, Pierre, Zoulim, Fabien, Hansen, Bettina, and Janssen, Harry L A

Published
2015
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162. Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters

Author

van der Meer, Adriaan J, Hansen, Bettina E, Fattovich, Giovanna, Feld, Jordan J, Wedemeyer, Heiner, Dufour, Jean-François, Lammert, Frank, Duarte-Rojo, Andres, Manns, Michael P, Ieluzzi, Donatella, Zeuzem, Stefan, Hofmann, Peter W, de Knegt, Robert J, Veldt, Bart J, and Janssen, Harry L A

Published
2015
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163. Increased prevalence of liver fibrosis in people living with HIV without viral hepatitis compared to population controls

Author

Kirkegaard-Klitbo, Ditte Marie, Bendtsen, Flemming, Lundgren, Jens, de Knegt, Robert J, Kofoed, Klaus Fuglsang, Nielsen, Susanne Dam, Benfield, Thomas, Kirkegaard-Klitbo, Ditte Marie, Bendtsen, Flemming, Lundgren, Jens, de Knegt, Robert J, Kofoed, Klaus Fuglsang, Nielsen, Susanne Dam, and Benfield, Thomas

Abstract

BACKGROUND: Liver fibrosis is associated with poor liver related outcomes and mortality. People living with HIV (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls.METHODS: Cross-sectional cohort study. We compared 342 PWH with 2,190 population controls aged 50-70 years. Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were computed by logistic regression.RESULTS: The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%), p<0.01). HIV infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR:1.84 (1.17;2.88), p<0.01); higher age (per decade, aOR:3.34 (1.81;6.18), p<0.01); ALT (per 10 IU/L, aOR:1.25 (1.05;1.49), p<0.01); BMI (per 1 kg/m 2, aOR:1.17 (1.05;1.29), p<0.01) and previous exposure to didanosine (per year aOR:2.26 (1,01;5.06), p=0.05).CONCLUSIONS: The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine and a positive HIV status was independently associated with higher odds of elevated LSM.

Published
2021

164. Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity

Author

Krassenburg, Lisette A.P., Maan, Raoel, Ramji, Alnoor, Manns, Michael P., Cornberg, Markus, Wedemeyer, Heiner, de Knegt, Robert J., Hansen, Bettina E., Janssen, Harry L.A., de Man, Robert A., Feld, Jordan J., van der Meer, Adriaan J., Krassenburg, Lisette A.P., Maan, Raoel, Ramji, Alnoor, Manns, Michael P., Cornberg, Markus, Wedemeyer, Heiner, de Knegt, Robert J., Hansen, Bettina E., Janssen, Harry L.A., de Man, Robert A., Feld, Jordan J., and van der Meer, Adriaan J.

Abstract

Background & Aims: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. Methods: Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. Results: In total, 868 patients were included with a median age of 59 (IQR 54–65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20–36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27–0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67–2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7–67.1 vs. 48.9%; 95% CI 38.1–59.7, respectively, p = 0.99). Conclusions: Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. Lay summary: Chronic HCV infection can be

Published
2021

165. The netherlands is on track to meet the world health organization hepatitis C elimination targets by 2030

Author

Van Dijk, Marleen, Brakenhoff, Sylvia M., Isfordink, Cas J., Cheng, Wei‐Han, Blokzijl, Hans, Boland, Greet, Dofferhoff, Anthonius S.M., Van Hoek, Bart, Van Nieuwkoop, Cees, Sonneveld, Milan J., Van Der Valk, Marc, Drenth, Joost P.H., De Knegt, Robert J., Van Dijk, Marleen, Brakenhoff, Sylvia M., Isfordink, Cas J., Cheng, Wei‐Han, Blokzijl, Hans, Boland, Greet, Dofferhoff, Anthonius S.M., Van Hoek, Bart, Van Nieuwkoop, Cees, Sonneveld, Milan J., Van Der Valk, Marc, Drenth, Joost P.H., and De Knegt, Robert J.

Abstract

Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well‐supported timeline towards HCV elimination in The Netherlands. Methods: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (≤5 per 100,000). Results: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO’s elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver‐related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liverrelated death from 2020-2030. Conclusions: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated.

Published
2021

166. The netherlands is on track to meet the world health organization hepatitis C elimination targets by 2030

Author

MS MDL 1, MMB Staf diagnostiek, Infection & Immunity, Van Dijk, Marleen, Brakenhoff, Sylvia M., Isfordink, Cas J., Cheng, Wei‐Han, Drenth, Joost P.H., De Knegt, Robert J., Blokzijl, Hans, Boland, Greet, Dofferhoff, Anthonius S.M., Van Hoek, Bart, Van Nieuwkoop, Cees, Sonneveld, Milan J., Van Der Valk, Marc, MS MDL 1, MMB Staf diagnostiek, Infection & Immunity, Van Dijk, Marleen, Brakenhoff, Sylvia M., Isfordink, Cas J., Cheng, Wei‐Han, Drenth, Joost P.H., De Knegt, Robert J., Blokzijl, Hans, Boland, Greet, Dofferhoff, Anthonius S.M., Van Hoek, Bart, Van Nieuwkoop, Cees, Sonneveld, Milan J., and Van Der Valk, Marc

Published
2021

168. Analysis of innate and adaptive host immunity during combination therapy with peginterferon Lambda-1a and Entecavir in patients with HBeAg(+) chronic hepatitis B: 219

Author

Phillips, Sandra, Mistry, Sameer, Riva, Antonio, Cooksley, Helen, Zeuzem, Stefan, Woffendin, Clive, Chen, Pei-Jer, Peng, Cheng-Yuan, Chang, Ting-Tsung, Lueth, Stefan, de Knegt, Robert J., Choi, Moon Seok, Wedemeyer, Heiner, Dao, Michael, Kim, Chang Wook, Chu, Heng C., Wind-Rotolo, Megan, Williams, Roger, Cooney, Elizabeth L., and Chokshi, Shilpa

Published
2014

173. Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity

Author

Krassenburg, Lisette A.P., primary, Maan, Raoel, additional, Ramji, Alnoor, additional, Manns, Michael P., additional, Cornberg, Markus, additional, Wedemeyer, Heiner, additional, de Knegt, Robert J., additional, Hansen, Bettina E., additional, Janssen, Harry L.A., additional, de Man, Robert A., additional, Feld, Jordan J., additional, and van der Meer, Adriaan J., additional

Published
2021
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174. Disease burden and management of Crigler‐Najjar syndrome: Report of a world registry.

Author

Aronson, Sem J., Junge, Norman, Trabelsi, Mediha, Kelmemi, Wided, Hubert, Aurelie, Brigatti, Karlla W., Fox, Michael D., de Knegt, Robert J., Escher, Johanna C., Ginocchio, Virginia M., Iorio, Raffaele, Zhu, Yan, Özçay, Figen, Rahim, Fakher, El‐Shabrawi, Mortada H.F., Shteyer, Eyal, Di Giorgio, Angelo, D'Antiga, Lorenzo, Mingozzi, Federico, and Brunetti‐Pierri, Nicola

Subjects
SKIN cancer, DISEASE management, CYSTIC fibrosis transmembrane conductance regulator
Abstract

We found in 31 patients with liver fibrosis evaluation (liver histology or Fibroscan) five patients (16%) with signs of advanced liver fibrosis. Keywords: encephalopathy; liver transplantation; phototherapy; UGT1A1; unconjugated hyperbilirubinemia EN encephalopathy liver transplantation phototherapy UGT1A1 unconjugated hyperbilirubinemia 1593 1604 12 06/27/22 20220701 NES 220701 Abbreviations ALT alanine aminotransferase AST aspartate aminotransferase CB conjugated bilirubin CNS Crigler-Najjar syndrome GGT gamma glutamyl transpeptidase PB phenobarbital PT phototherapy TB total bilirubin UCB unconjugated bilirubin UGT1A1 uridine 5'-diphosphate glucuronosyltransferase ULN upper limit of normal Abstract Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. That in our small subcohort of fibrosis evaluated patients only patient with PT showed fibrosis is most likely caused because of the more severe phenotype in these patients but an association between long-term PT use and development of fibrosis cannot be excluded based on our data. Better detection and characterizing of liver fibrosis in CNS patients is necessary to gain an understanding of aetiology, to identify patients at risk, to develop individual treatment plans (e.g. LT vs. gene therapy in the future) and to probably find a way to avoid the development of fibrosis. [Extracted from the article]

Published
2022
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175. Very low probability of significant liver inflammation in chronic hepatitis B patients with low ALT levels in the absence of liver fibrosis

Author

Sonneveld, Milan J., Brouwer, Willem P., Hansen, Bettina E., Chan, Henry L.Y., Piratvisuth, Teerha, Jia, Ji Dong, Zeuzem, Stefan, Chien, Rong Nan, Choi, Hannah, de Knegt, Robert J., Wat, Cynthia, Pavlovic, Vedran, Gaggar, Anuj, Xie, Qing, Buti, Maria, de Man, Robert A., Janssen, Harry L.A., and Gastroenterology & Hepatology

Subjects
Adult, Inflammation, Liver Cirrhosis, Male, Probability of Serious Inflammation in Chronic Hbv Infection, Biopsy, Alanine Transaminase, Middle Aged, Prognosis, Hepatitis, Cohort Studies, Young Adult, Hepatitis B, Chronic, SDG 3 - Good Health and Well-being, Risk Factors, Humans, Original Article, Female, Probability
Abstract

Summary Background Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment. Aim To study rates and determinants of clinically significant liver inflammation. Methods We selected patients with HBV DNA > 2000 IU/mL from the SONIC‐B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2). Results The cohort included 2991 patients; 1672 were HBeAg‐positive. ALT was 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P 2 times ULN (P

Published
2020

177. Clinical Implementation of Single-Cell RNA Sequencing Using Liver Fine Needle Aspirate Tissuesampling and Centralized Processing Captures Compartment Specific Immuno-Diversity

Author

Genshaft, Alex S., primary, Subudhi, Sonu, additional, Keo, Arlin, additional, Sanchez Vasquez, Juan D., additional, Conceição-Neto, Nádia, additional, Mahamed, Deeqa, additional, Boeijen, Lauke L., additional, Alatrakchi, Nadia, additional, Oetheimer, Chris, additional, Vilme, Mike, additional, Drake, Riley, additional, Fleming, Ira, additional, Tran, Nancy, additional, Tzouanas, Constantine, additional, Joseph-Chazan, Jasmin, additional, Arreola Villanueva, Martin, additional, van de Werken, Harmen J. G., additional, van Oord, Gertine W., additional, Groothuismink, Zwier M.A., additional, Beudeker, Boris J., additional, Osmani, Zgjim, additional, Nkongolo, Shirin, additional, Mehrotra, Aman, additional, Feld, Jordan, additional, Chung, Raymond T., additional, de Knegt, Robert J., additional, Janssen, Harry L.A., additional, Aerssens, Jeroen, additional, Bollekens, Jacques, additional, Hacohen, Nir, additional, Lauer, Georg M., additional, Boonstra, Andre, additional, Shalek, Alex, additional, and Gehring, Adam J., additional

Published
2021
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188. Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss

Author

Brakenhoff, Sylvia M., primary, de Man, Robert A., additional, Boonstra, André, additional, van Campenhout, Margo J. H., additional, de Knegt, Robert J., additional, van Bömmel, Florian, additional, van der Eijk, Annemiek A., additional, Berg, Thomas, additional, Hansen, Bettina E., additional, Janssen, Harry L. A., additional, and Sonneveld, Milan J., additional

Published
2020
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189. Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

Author

Karabegović, Irma, primary, Portilla-Fernandez, Eliana, additional, Li, Yang, additional, Ma, Jiantao, additional, Maas, Silvana C.E., additional, Sun, Daokun, additional, Hu, Emily A., additional, Kühnel, Brigitte, additional, Zhang, Yan, additional, Ambatipudi, Srikant, additional, Fiorito, Giovanni, additional, Huang, Jian, additional, Castillo-Fernandez, Juan E., additional, Wiggins, Kerri L., additional, de Klein, Niek, additional, Grioni, Sara, additional, Swenson, Brenton R., additional, Polidoro, Silvia, additional, Treur, Jorien L., additional, Cuenin, Cyrille, additional, Tsai, Pei-Chien, additional, Costeira, Ricardo, additional, Chajes, Veronique, additional, Braun, Kim, additional, Verweij, Niek, additional, Kretschmer, Anja, additional, Franke, Lude, additional, van Meurs, Joyce B.J., additional, Uitterlinden, André G., additional, de Knegt, Robert J., additional, Ikram, M. Arfan, additional, Dehghan, Abbas, additional, Peters, Annette, additional, Schöttker, Ben, additional, Gharib, Sina A., additional, Sotoodehnia, Nona, additional, Bell, Jordana T., additional, Elliott, Paul, additional, Vineis, Paolo, additional, Relton, Caroline, additional, Herceg, Zdenko, additional, Brenner, Hermann, additional, Waldenberger, Melanie, additional, Rebholz, Casey M., additional, Voortman, Trudy, additional, Pan, Qiuwei, additional, Fornage, Myriam, additional, Levy, Daniel, additional, Kayser, Manfred, additional, and Ghanbari, Mohsen, additional

Published
2020
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198. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Author

Ginès, Pere, Castera, Laurent, Lammert, Frank, Graupera, Isabel, Serra‐Burriel, Miquel, Allen, Alina M., Wong, Vincent Wai‐Sun, Hartmann, Phillipp, Thiele, Maja, Caballeria, Llorenç, de Knegt, Robert J., Grgurevic, Ivica, Augustin, Salvador, Tsochatzis, Emmanuel A., Schattenberg, Jörn M., Guha, Indra Neil, Martini, Andrea, Morillas, Rosa M., Garcia‐Retortillo, Montserrat, and de Koning, Harry J.

Published
2022
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