tbuckley/cabot-search huggingface dataset:
Trastuzumab-MC-vc-PAB-MMAF: The effects of the Drug:Antibody Ratio (DAR) on efficacy, toxicity and pharmacokinetics.
Authors: Douglas Leipold, Nelson Jumbe, Debra Dugger, Lisa Crocker, Will Leach, Mark Sliwkowski, Damon Meyer, Peter Senter, Jay Tibbitts
Journal: Cancer Research (2007)

1551  Trastuzumab-MC-vc-PAB-MMAF (Trastuzumab-vc-MMAF) is a humanized monoclonal antibody (Herceptin®, trastuzumab, Tmab) conjugated through a protease-sensitive valine-citrulline dipeptide linker with a monomethyl auristatin E phenylalanine drug (MMAF). MMAF is an anti-mitotic agent, inhibiting tubulin polymerization, resulting in cell death.  Trastuzumab-vc-MMAF, and antibody drug conjugates in general, can be characterized by the drug:antibody ratio (DAR), which represents a distribution of drugs (MMAF molecules) on the antibody. The conjugation occurs through reduction/oxidation of the inter-chain disulfide bonds, and depending upon the completeness of the reaction can result in a DAR from 0 to 8 (2 MMAF molecules per disulfide bond). With this distribution, we cannot adequately assess the role and importance of the DAR in the Trastuzumab-vc-MMAF program. Therefore, to assess the effect of the DAR in-vivo, Trastuzumab-vc-MMAF was purified as three separate lots with a DAR = 2, DAR = 4, and DAR = 6.  The effect of DAR on efficacy was assessed in the Fo5 and the BT474EEI xenograft models. Whether dose was normalized upon dose of MMAF administered (µg/m2) or normalized upon antibody dose (mg/kg), Trastuzumab-vc-MMAF demonstrated a tumor response that directly correlated with antibody dose and was independent of MMAF exposure.  In toxicity studies, the effect of DAR was assessed in naive Sprague-Dawley rats, and when normalized for MMAF exposure, the toxicity response was inversely correlated with antibody dose.  The effect of DAR on pharmacokinetics were assessed in naive Beige nude XID mice and Sprague-Dawley rats as single doses. Samples were measured by two ELISA assays, which determined both the amount of Trastuzumab regardless of conjugation status (Total trastuzumab) and the Trastuzumab-vc-MMAF measured as any trastuzumab molecule with at least one MMAF conjugated to the antibody. For total trastuzumab, the pharmacokinetics suggest that increasing DAR leads to increasing clearance, while trastuzumab-vc-MMAF clearance was determined by contribution of parallel elimination processes of loss of MMAF and normal antibody clearance mechanisms (e.g. FcRγ).  This data taken together suggests that DAR has a significant impact on efficacy, toxicity and PK and understanding these relationships will afford ideal design of antibody-drug conjugates.
Cytogenetic and Molecular Characterization of Genitourinary Extramedullary Disease in Acute Myeloid Leukemia
Authors: Kathy M. Tran, Hagop M. Kantarjian, Syed M. Kazmi, Alfonso Quintás-Cardama, Jorge E. Cortes, Zeev Estrov, Maro Ohanian, Tapan M. Kadia, Gautam Borthakur, Farhad Ravandi, Naveen Pemmaraju
Journal: Blood (2012)
Differential Cytokine Profiles in Patients with Hepatocellular Carcinoma Related to Hepatitis B Virus and Hepatitis C Virus Infection
Authors: J. Estevez, V.L. Chen, O. Podlaha, B. Li, A. Le, P. Vutien, E. Chang, Z. Jiang, S. Pflanz, D. Ge, A. Gaggar, M.H. Nguyen
Journal: Journal of Hepatology (2016)
MIR-21 and MIR-150 Downregulation is Associated with Oxaliplatin-Related Sinusoidal Obstruction Syndrome and Impaired Survival
Authors: J. Zhao, S. Rensen, C. Vreuls, M. van den Broek, A. Driessen, M. van Herwijnen, M. Jetten, D. Jennen, C. Dejong, S.O. Damink
Journal: Journal of Hepatology (2016)
Fish detection and characterization of IgA-mediated translocations in B-cell malignancies
Authors: Iwona Wlodarska, Michel Stul, L Michaux, Christiane Peeters, Ruth Achten, B Schlegelberger, C Bastard, C Bilhou-Nabera, HC Klobeck, Herman Van den Berghe, Anne Hagemeijer-Hausman
Journal: Blood (1999)
Re-Expression of Fetal Igf2 as Epidriver and Target for Therapy in Hcc
Authors: I. Martínez-Quetglas, R. Pinyol, D. Dauch, S. Torrecilla, V. Tovar, A. Moeini, C. Alsinet, S. Bonilla, A. Portela, L. Rodriguez-Carunchio, M. Solé, A. Villanueva, M. Esteller, L. Zender, J.M. Llovet
Journal: Journal of Hepatology (2016)
Preclinical Characterization of Potent Core Protein Assembly Modulators for the Treatment of Chronic Hepatitis B
Authors: Q. Huang, A. Mercier, Y. Zhou, K. Henne, G. Renuka Kumar, S. Sun, L. Guo, J. Liu, Y. Zong, T. Sun, K. Nabel, P.-C. Li, C. Mahon, G. Chen, M. Bures, L. Li, E. May, E. Connelly, J. Deer, S. Katen, S. Francis, W.W. Turner, A. Zlotnick, L.D. Arnold, U. Lopatin
Journal: Journal of Hepatology (2016)
Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir are Safety and Eficacy for Treating HCV GT1 and 4 Infection in Patients with Severe Renal Impairment or End-Stage Renal Disease: A Mulcicenter Experience
Authors: R.M. Gómez, D. Rincón, E. Hernández, A. Ahumada, M.D. Pérez Valderas, M.J. Devesa, F. Cuenca, C. Fernández, M.L. Gutierrez, M. Ortiz, M. Calvo, G. Castellano, I. Fernández
Journal: Journal of Hepatology (2016)
<i>Update</i>: Influenza Activity — United States and Worldwide, May 21–September 23, 2017
Authors: Lenee Blanton, David E. Wentworth, Noreen Alabi, Eduardo Azziz-Baumgartner, John Barnes, Lynnette Brammer, Erin Burns, C. Todd Davis, Vivien G. Dugan, Alicia M. Fry, Rebecca Garten, Lisa A. Grohskopf, Larisa Gubareva, Krista Kniss, Stephen Lindstrom, Desiree Mustaquim, Sonja J. Olsen, Katherine Roguski, Calli Taylor, Susan Trock, Xiyan Xu, Jacqueline Katz, Daniel Jernigan
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

During May 21-September 23, 2017,* the United States experienced low-level seasonal influenza virus activity; however, beginning in early September, CDC received reports of a small number of localized influenza outbreaks caused by influenza A(H3N2) viruses. In addition to influenza A(H3N2) viruses, influenza A(H1N1)pdm09 and influenza B viruses were detected during May-September worldwide and in the United States. Influenza B viruses predominated in the United States from late May through late June, and influenza A viruses predominated beginning in early July. The majority of the influenza viruses collected and received from the United States and other countries during that time have been characterized genetically or antigenically as being similar to the 2017 Southern Hemisphere and 2017-18 Northern Hemisphere cell-grown vaccine reference viruses; however, a smaller proportion of the circulating A(H3N2) viruses showed similarity to the egg-grown A(H3N2) vaccine reference virus which represents the A(H3N2) viruses used for the majority of vaccine production in the United States. Also, during May 21-September 23, 2017, CDC confirmed a total of 33 influenza variant virus
The Significant Association between Controlled Attenuation Parameter Assessed by Transient Elastography and Visceral Fat, Not Body Mass Index
Authors: L.H. Won, K.K. Joon, C.K. Sik, C.Y. Eun, K.B. Kyung, K.S. Up, K. Do Young, A.S. Hoon, H. Kwang-Hyub, P.J. Yong
Journal: Journal of Hepatology (2016)
Invasive Fungal Infections in Pediatric Acute Lymphoblastic Leukemia: Incidence, Characterization, Outcome and Risk Analysis of Study ALL-BFM 2000
Authors: Georg Mann, Andishe Attarbaschi, Martin Schrappe, Anja Möricke, Kirsten Bleckmann, Julia Alten, Thomas Lehrnbecher, Martin Zimmermann, Felix Niggli
Journal: Blood (2014)
Human CalDAG-GEFI deficiency increases bleeding and delays αIIbβ3 activation
Authors: Hisashi Kato, Yozo Nakazawa, Yumi Kurokawa, Hirokazu Kashiwagi, Yoichiro Morikawa, Daisuke Morita, Fumiaki Banno, Shigenori Honda, Yuzuru Kanakura, Yoshiaki Tomiyama
Journal: Blood (2016)
A Sneeze
Authors: Lydia Bourouiba
Journal: New England Journal of Medicine (2016)

A human sneeze can eject droplets of fluid and potentially infectious organisms.The image sequence captures, in increments of 20 msec, the emission of a sneeze cloud produced by a healthy person.The sneeze was produced naturally, without the introduction of additives, colorants, or contaminants for visualization.High-speed video (Video 1, normal speed; Video 2, slowed down by a factor of 67), recorded at 1000 frames per second, shows a turbulent cloud that consists of hot and moist exhaled air, mucosalivary filaments and drops, and residues from droplet evaporation (nuclei).The ejection lasts up to 150 msec (top row) and then transitions into a freely evolving turbulent puff cloud (middle and bottom rows).The largest droplets rapidly settle within 1 to 2 m away from the person.The smaller and evaporating droplets are trapped in the turbulent puff cloud, remain suspended, and, over the course of seconds to a few minutes, can travel the dimensions of a room and land up to 6 to 8 m away.
Mathematical Models of Contrast Transport Kinetics for Cancer Diagnostic Imaging: A Review
Authors: Simona Turco, Hessel Wijkstra, Massimo Mischi
Journal: IEEE Reviews in Biomedical Engineering (2016)

Angiogenesis plays a fundamental role in cancer growth and the formation of metastasis. Novel cancer therapies aimed at inhibiting angiogenic processes and/or disrupting angiogenic tumor vasculature are currently being developed and clinically tested. The need for earlier and improved cancer diagnosis, and for early evaluation and monitoring of therapeutic response to angiogenic treatment, have led to the development of several imaging methods for in vivo noninvasive assessment of angiogenesis. The combination of dynamic contrast-enhanced imaging with mathematical modeling of the contrast agent kinetics enables quantitative assessment of the structural and functional changes in the microvasculature that are associated with tumor angiogenesis. In this paper, we review quantitative imaging of angiogenesis with dynamic contrast-enhanced magnetic resonance imaging, computed tomography, and ultrasound.
Factors Impacting SVR12 for Patients with Advanced Cirrhosis Receiving Daclatasvir and Sofosbuvir with Ribavirin in the Ally-1 Study
Authors: F. Poordad, R. Fontana, E. Schiff, J.M. Vierling, C. Landis, Y. Zhao, Y. Gandhi, T. Garimella, T. Eley, S. Noviello, E.S. Swenson
Journal: Journal of Hepatology (2016)
Heritable components of the human fecal microbiome are associated with visceral fat
Authors: Michelle Beaumont, Julia K. Goodrich, Matthew A. Jackson, Idil Yet, Emily R. Davenport, Sara Vieira-Silva, Justine Debelius, Tess Pallister, Massimo Mangino, Jeroen Raes, Rob Knight, Andrew G. Clark, Ruth E. Ley, Tim D. Spector, Jordana T. Bell
Journal: Genome biology (2016)

Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies.
Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial
Authors: Vanita R. Aroda, Julio Rosenstock, Carol Wysham, Jeffrey Unger, Diego Bellido, Guillermo González-Gálvez, Akane Takami, Hailing Guo, Elisabeth Niemoeller, Elisabeth Souhami, Richard M. Bergenstal
Journal: Diabetes Care (2016)

OBJECTIVE This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. RESEARCH DESIGN AND METHODS After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose &amp;lt;100 mg/dL (&amp;lt;5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks. RESULTS HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (–1.1% vs. –0.6%, P &amp;lt; 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c &amp;lt;7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P &amp;lt; 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. CONCLUSIONS Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.
Risk Factors For The Development Of Severe Bacterial Infection In Patients With Multiple Myeloma During Chemotherapy With Bortezomib Containing Regimens
Authors: Shin Young Hyun, Ji Eun Jang, Yundeok Kim, Doh Yu Hwang, Soo Jeong Kim, Yu Ri Kim, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
Journal: Blood (2013)
Efficacy and Tolerability of Interferon-Free Antiviral Therapy in Kidney Transplant (KT) Recipients with Chronic Hepatitis C: Real-Life Data from the Spanish National Registry (HEPA-C)
Authors: M.-C. Londoño, I. Fernández, R. Muñoz-Gómez, J.-M. Pascasio, C. Baliellas, N. Polanco, N. Esforzado, M. Prieto, L. Castells, J. Crespo, J.-L. Calleja, F. Gea, X. Forns
Journal: Journal of Hepatology (2016)
Similar Frequencies, Phenotype and Activation Status of Intrahepatic NK Cells in Chronic HBV Patients after Long-Term Treatment with Tenofovir Disoproxil Fumarate (TDF)
Authors: L.L. Boeijen, M.J. van Campenhout, E.T. Tjwa, R. Zoutendijk, G.W. van Oord, R.J. de Knegt, H.L. Janssen, A.M. Woltman, A. Boonstra
Journal: Journal of Hepatology (2016)
Enteropathy-Associated T-Cell Lymphoma Type I, But Not Refractory Celiac Disease, Strongly Expresses CD30 and Might Benefit From Brentuximab Vedotin
Authors: David Sibon, Georgia Malamut, Virginie Verkarre, Coralie Derrieux, Isabelle Radford, Bertrand Meresse, Elizabeth Macintyre, Christophe Cellier, Nadine Cerf-Bensussan, Nicole Brousse, Olivier Hermine
Journal: Blood (2013)
Alternative Splicing and Expression of Class II Tubulin Beta (TUBB2B) Are Associated with Outcome in Diffuse Large B-Cell Lymphoma
Authors: Minna Taskinen, Satu Koivula, Ping Chen, Marja-Liisa Karjalainen-Lindsberg, Alejandra Cervera, Jan Delabie, Harald Holte, Sampsa Hautaniemi, Sirpa Leppä
Journal: Blood (2012)
Multipeptide pancreatic cancer immunotherapy and immunomodulation.
Authors: Juan Pablo Marquez-Manriquez, Mark Verburg, Jose Antonio Matute-Briseno, Erik Ramos, Imelda Lopez-Molina, Rosana Soto, Daniel Herendeen, Kenneth Quayle, Guadalupe Arturo Vega-Garcia, Gerardo Palacios Diaz De Leon, Gabriela Borquez-Lopez, Fernando ALFONSO Durazo-Bustamante, Arturo Suplee-Rivera, Sara Carrillo-Marquez, Pedro Alejandro Lucero-Diaz
Journal: Journal of Clinical Oncology (2016)

e15705 Background: The discovery of biological relevant targets to design effective active antigen specific immunotherapy for pancreatic ductal adenocarcinoma (PDAC) is extremely important. In terms of active antigen specific immunotherapy, it is important to consider the addition of immunomodulatory approaches such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). We evaluated whether seven aberrantly expressed proteins associated with bad prognosis could be immunogenic in peripheral blood mononuclear cells (PBMC) from patients with PDAC. Also we performed the immunogenicity studies in mice to find the best IFN-gamma producing peptides derived from seven proteins. Finally we added anti-CTLA-4 inhibitor so see if we can improve the observed in vitroresponses. Methods: Predicted peptides from Bcl-2XL , ABCG2, PTP4A3, Sox9, APLP2, VCP and Mcl-2 were tested by IFN-gamma ELISPOT in PDAC PBMC patients with 100 % Karnofsky (n = 10) and matched controls (n = 10). Also the peptides were evaluated in mice for immunogenicity studies using ELISA and ELISPOT. Additionally we tested if the best peptides can improve the magnitude of the IFN-gamma responses by adding escalated doses in vitroof ipilimumab. Results: Some predicted peptides were significantly elevated in PDAC PBMC when compared with donors controls (Bcl-2XL p = 0.005, ABCG2 p = 0.0001, PTP4A3 p = 0.005, Sox9 p = 0.0001, APLP2 p = 0.001, VCP p = 0.0017 and Mcl-1 p = 0.0001. IFN-gamma immune responses were significant in mice immunized with Bcl-XL p = 0.001, ABCG2 p = 0.001 and PTP4A3 p = 0.005. The combination in vitrowith ipilimumab and multi-peptide vaccination increased IFN-gamma production (p = 0.0001). Conclusions: PDAC contains overexpressed proteins that can serve as targets for active antigen specific immunotherapy. These data will serve as a proof of principle to start evaluating the best immunogenic peptides in PDAC animal models and validate the human ELISPOT studies in a large cohort of PDAC patients. Combinatorial immunotreatment for PDAC could be feasible in active disease and potentially for relapse prevention.
Surveillance de la tuberculose dans la Région Europe de l'OMS, 1995-1996
Authors: D Antoine, V Schwoebel, J Veen, M. C. Raviglione, H. L. Rieder
Journal: Eurosurveillance (1998)

Cree en 1996, le projet EuroTB pour la surveillance de la tuberculose (TB) en Europe a pour objectif de recueillir, analyser et diffuser des donnees sur les cas de tuberculose declares dans la Region Europe de l'Organisation Mondiale de la Sante (OMS). Suite a une etude de faisabilite menee en 1996-1997 portant sur les cas declares en 1995 (1), un systeme regulier de recueil de donnees a ete mis en place. Le projet est pilote conjointement par le Centre Europeen pour la Surveillance Epidemiologique du SIDA (CESES) a Saint-Maurice, France, et la Royal Netherlands Tuberculosis Association (KNCV) a La Haye, Pays-Bas.
Overexpression of Mirna-506 in Human Cholangiocytes Causes Primary Biliary Cholangitis-Like Features including Mitochondrial Dysfunction and Increased Sensitivity to Apoptosis
Authors: O. Erice, P. Munoz-Garrido, J. Vaquero, M.J. Perugorria, M.G. Fernandez-Barrena, E. Sáez, A. Arbelaiz, Á. Santos-Laso, R. Jimenez-Agüero, J. Fernandez-Irigoyen, E. Santamaria, V. Torrano, A. Carracedo, M. Marzioni, J. Prieto, U. Beuers, R.O. Elferink, N.F. LaRusso, L. Bujanda, J.J.G. Marin, J.M. Banales
Journal: Journal of Hepatology (2016)
Obeticholic Acid Ameliorates Non-Alcoholic Fatty Liver Disease by Improving Metabolic Profile in Dietary Obesity, but Not in Obese, Diabetic FOZ/FOZ Mice
Authors: F. Haczeyni, L. Poekes, V. Barn, A.R. Mridha, W.G. Haigh, G.N. Ioannou, M.M. Yeh, I.A. Leclercq, N.C. Teoh, G.C. Farrell
Journal: Journal of Hepatology (2016)
In-vitro activity of the multi-targeted receptor tyrosine kinase inhibitor sunitinib malate (SU11248) against gastrointestinal stromal tumor (GIST) mutants refractory to imatinib mesylate
Authors: Hans Prenen, Jan Cools, Nicole Mentens, Raphael Sciot, Patrick Schöffski, Allan Van Oosterom, Peter Marynen, Maria Debiec-Rychter
Journal: Clinical Cancer Research (2005)
Real-Life Outcomes of 8 Weeks Regimen of Sofosbuvir and Ledipasvir without Ribavirin, in Non-Cirrhotic Treatment-Naïve Hepatitis C Genotype 1 Patients with less than 6 Million IU/ML Viral Load
Authors: K. Qureshi, J. Andres, J. Regester, S. Lott, J. Halladay, C. Peleckis, P. Urick
Journal: Journal of Hepatology (2016)
Baveno VI Recommendation on Avoidance of Screening Endoscopy in Cirrhotic Patients based on Liver Elastography and Platelet Count – Are We There Yet?
Authors: M.J. Silva, P. Duarte, M. Mendes, C. Bernardes, J. Pinto, R. Loureiro, J. Esteves, F. Calinas
Journal: Journal of Hepatology (2016)
Optimization of in vivo DNA delivery with NickFect peptide vectors
Authors: Krista Freimann, Piret Arukuusk, Kaido Kurrikoff, Luís Daniel Ferreira Vasconcelos, Kadi-Liis Veiman, Julia Uusna, Helerin Margus, Alfonso T. Garcia-Sosa, Margus Pooga, Ülo Langel
Journal: Journal of Controlled Release (2016)
Bi- and Trispecific Antibody Constructs Mediate Specific T-Cell Retargeting Towards and Elimination of HBV-Positive Hepatocytes and Tumor Cells
Authors: F. Bohne, O. Quitt, J. Hasreiter, S. Luo, J.-H. Bockmann, R. Tedjokusumo, F. Momburg, U. Protzer
Journal: Journal of Hepatology (2016)