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2. Corrigendum to: “Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results” [JHEP Reports 5 (2019) 101041]

Author

van Baar, Annieke C.G., primary, Beuers, Ulrich, additional, Wong, Kari, additional, Haidry, Rehan, additional, Costamagna, Guido, additional, Hadefi, Alia, additional, Deviere, Jacques, additional, Ghosh, Soumitra S., additional, Lopez-Talavera, Juan Carlos, additional, Rodriguez, Leonardo, additional, Galvao Neto, Manoel P., additional, Sanyal, Arun, additional, and Bergman, Jacques J.G.H.M., additional

Published
2024
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5. Islet Growth Factors

Author

Vasavada, Rupangi C., Garcia-Ocaña, Adolfo, Takane, Karen K., Cebrian, Ana, Lopez-Talavera, Juan Carlos, Stewart, Andrew F., Conn, P. Michael, editor, and Sperling, Mark A., editor

Published
2003
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6. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial

Author

Mingrone, Geltrude, Baar, Annieke C.G. van, Hopkins, David, Moura, Eduardo G.H. de, Cercato, Cintia, Rajagopalan, Harith, Lopez-Talavera, Juan Carlos, White, Kelly, Bhambhani, Vijeta, Costamagna, Guido, Haidry, Rehan, Grecco, Eduardo, Aithal, Guruprasad P, Repici, Alessandro, Hayee, Bu, Haji, Amyn, Morris, A John, Bisschops, Raf, Chouhan, Manil D., Sakai, Naomi S., Bhatt, Deepak L., Sanyal, Arun J., and Bergman, Jacques J.G.H.M.

Subjects
embryonic structures, Duodenal mucosal resurfacing, DMR, endoscopic procedure, non-alcoholic fatty liver disease, NAFLD, type 2 diabetes, T2D, Revita system
Abstract

Objective: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority RCT, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR [catheter and system], on glycaemic control and liver fat content in Type 2 Diabetes (T2D).Design: Eligible patients (HbA1c 59–86mmol/mol, BMI ≥24 and ≤40kg/m2, fasting insulin >48.6pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver magnetic resonance imaging proton-density fat fraction (MRI-PDFF) at 12 weeks. Results: Overall mITT (DMR N=56; sham N=52), 24-weeks post-DMR, median (IQR) HbA1c change was −10.4 (18.6) mmol/mol in DMR group versus −7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was −5.4 (5.6)% in DMR group versus −2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR N=39; sham N=37) and Brazilian (DMR N=17; sham N=16) populations (p=0.063), therefore, results were stratified by region. In European mITT, 24-weeks post-DMR, median (IQR) HbA1c change was –6.6 mmol/mol (17.5 mmol/mol) versus –3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was –5.4% (6.1%) versus –2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ([FPG] ≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. Conclusions: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease (NAFLD), particularly in patients with high FPG.

Published
2022

11. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: The randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial

Author

Mingrone, Geltrude, van Baar, Annieke A.C., Devière, Jacques, Hopkins, David, Moura, Eduardo, Cercato, Cintia, Rajagopalan, Harith, Lopez-Talavera, Juan Carlos, White, Kelly, Bhambhani, Vijeta, Costamagna, Guido, Haidry, Rehan R.J., Grecco, Eduardo, Galvao Neto, Manoel M.P., Aithal, Guruprasad P, Repici, Alessandro, Hayee, Bu'Hussain, Haji, Amyn, Morris, Allan John, Bisschops, Raf, Chouhan, Manil M.D., Sakai, Naomi N.S., Bhatt, Deepak D.L., Sanyal, Arun Jayant, Bergman, Jacques J.J.G.H.M., Mingrone, Geltrude, van Baar, Annieke A.C., Devière, Jacques, Hopkins, David, Moura, Eduardo, Cercato, Cintia, Rajagopalan, Harith, Lopez-Talavera, Juan Carlos, White, Kelly, Bhambhani, Vijeta, Costamagna, Guido, Haidry, Rehan R.J., Grecco, Eduardo, Galvao Neto, Manoel M.P., Aithal, Guruprasad P, Repici, Alessandro, Hayee, Bu'Hussain, Haji, Amyn, Morris, Allan John, Bisschops, Raf, Chouhan, Manil M.D., Sakai, Naomi N.S., Bhatt, Deepak D.L., Sanyal, Arun Jayant, and Bergman, Jacques J.J.G.H.M.

Abstract

Objective: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). Design: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. Results: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. Conclusions: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, part, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

12. Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection

Author

Rao, Huiying, Wei, Lai, Lopez-Talavera, Juan Carlos, Shang, Jia, Chen, Hong, Li, Jun, Xie, Qing, Gao, Zhiliang, Wang, Lei, Wei, Jia, Jiang, Jianning, Sun, Yongtao, Yang, Ruifeng, Li, Hong, Zhang, Haiying, Gong, Zuojiong, Zhang, Lunli, Zhao, Longfeng, Dou, Xiaoguang, Niu, Junqi, You, Hong, Chen, Zhi, Ning, Qin, Gong, Guozhong, Wu, Shuhuan, Ji, Wei, Mao, Qing, Tang, Hong, Li, Shuchen, Wei, Shaofeng, Sun, Jian, Jiang, Jiaji, Lu, Lungen, Jia, Jidong, and Zhuang, Hui

Published
2014
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13. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial

Author

Mingrone, Geltrude, primary, van Baar, Annieke CG, additional, Devière, Jacques, additional, Hopkins, David, additional, Moura, Eduardo, additional, Cercato, Cintia, additional, Rajagopalan, Harith, additional, Lopez-Talavera, Juan Carlos, additional, White, Kelly, additional, Bhambhani, Vijeta, additional, Costamagna, Guido, additional, Haidry, Rehan, additional, Grecco, Eduardo, additional, Galvao Neto, Manoel, additional, Aithal, Guruprasad, additional, Repici, Alessandro, additional, Hayee, Bu'Hussain, additional, Haji, Amyn, additional, Morris, A John, additional, Bisschops, Raf, additional, Chouhan, Manil D, additional, Sakai, Naomi S, additional, Bhatt, Deepak L, additional, Sanyal, Arun J, additional, and Bergman, J J G H M, additional

Published
2021
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22. 121-LB: Durable Glycemic Improvements after Duodenal Mucosal Resurfacing (DMR) in Patients with Type 2 Diabetes (T2D): 48-Week Results from the REVITA-2 European Cohort

Author

MINGRONE, GELTRUDE, primary, HOPKINS, DAVID, additional, AITHAL, GURUPRASAD, additional, COSTAMAGNA, GUIDO, additional, CRENIER, LAURENT, additional, DEVIERE, JACQUES M., additional, DRUMMOND, RUSSELL, additional, HAIDRY, REHAN, additional, I, ISKANDAR R., additional, LANIA, ANDREA, additional, MAGEE, CORMAC, additional, NIEUWDORP, MAX, additional, BHAMBHANI, VIJETA, additional, HUANG, JASON, additional, WHITE, KELLY, additional, LOPEZ-TALAVERA, JUAN CARLOS, additional, RAJAGOPALAN, HARITH, additional, and BERGMAN, JACQUES J., additional

Published
2020
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23. OR30-07 Mixed Meal Tolerance Test (MMTT) Results from Revita-2, the First Randomized, Sham-Controlled, Double-Blind, Prospective, Multicenter Study of Duodenal Mucosal Resurfacing (DMR) Safety and Efficacy in Patients with Sub-Optimally Controlled Type 2 Diabetes (T2D)

Author

Hopkins, David, primary, Mingrone, Geltrude, primary, Aithal, Guruprasad P, primary, Bhambhani, Vijeta, primary, Costamagna, Guido, primary, Crenier, Laurent, primary, Deviere, Jacques, primary, Drummond, Russell Sinclair, primary, Haidry, Rehan, primary, Idris, Iskandar, primary, Lania, Andrea, primary, Lopez-Talavera, Juan Carlos, primary, Magee, Cormac, primary, Nieuwdorp, Max, primary, Rajagopalan, Harith, primary, White, Kelly, primary, and Bergman, Jacques J G H M, primary

Published
2020
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26. Proximal and Distal Gut Mucosa Adapt Differently to Westernized Diet, Promoting an Insulin-Resistant Dysmetabolic State

Author

West, Jason A., Tsakmaki, Anastasia, Huang, Jason H. S., Ghosh, Soumitra S., Parkes, David G., Wismann, Pernille, Rigbolt, Kristoffer T. G., Pedersen, Philip J., Pavlidis, Polychronis, Maggs, David, Lopez-Talavera, Juan Carlos, Bewick, Gavin A., and Rajagopalan, Harith

Abstract

SUMMARY The intestine adapts to local nutrient exposure, but little is known about the effect of high-fat diets (HFDs) on topographically distinct segments of the gut. Here, we show obesogenic diets induce different effects on proximal versus distal intestinal mucosa in vivo and mouse and human organoid models. Notably, we demonstrate proximal gut hyperplasia and distal gut hypoplasia in response to HFD in rodents and show that surgical and pharmacologic interventions that circumvent this altered mucosal physiology improve glucose metabolism. In addition, organoids derived from the duodenum of mice or humans demonstrate increased stemness (self-renewal and differentiation) and growth response to increasing amounts of lipid or glucose, while ileal organoids displayed a functionally different and often opposite growth response profile. These results highlight the important role of the small intestinal mucosa in regulating metabolic homeostasis in health and disease and open new avenues and therapeutic approaches to treat metabolic diseases. GRAPHICAL ABSTRACT

Published
2019
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29. Transgenic overexpression of hepatocyte growth factor in the β-cell markedly improves islet function and islet transplant outcomes in mice

Author

Garcia-Ocana, Adolfo, Vasavada, Rupangi C., Cebrian, Ana, Reddy, Vasumathi, Takane, Karen K., Lopez-Talavera, Juan-Carlos, and Stewart, Andrew F.

Subjects
Glucose tolerance tests -- Research -- Health aspects, Type 1 diabetes -- Health aspects -- Research, Diabetes -- Research, Health, Research, Health aspects
Abstract

Recent advances in human islet transplantation have highlighted the need for expanding the pool of β-cells available for transplantation. We have developed three transgenic models in which growth factors (hepatocyte growth factor [HGF], placental lactogen, or parathyroid hormone-related protein) have been targeted to the β-cell using rat insulin promoter (RIP). Each displays an increase in islet size and islet number, and each displays insulin-mediated hypoglycemia. Of these three models, the RIP-HGF mouse displays the least impressive phenotype under basal conditions. In this study, we show that this mild basal phenotype is misleading and that RIP-HGF mice have a unique and salutary phenotype. Compared with normal islets, RIP-HGF islets contain more insulin per β-cell (50 ± 5 vs. 78 ± 9 ng/islet equivalent [IE] in normal vs. RIP-HGF islets, P < 0.025), secrete more insulin in response to glucose in vivo (0.66 ± 0.06 vs. 0.91 ± 0.10 ng/ml in normal vs. RIP-HGF mice, P < 0.05) and in vitro (at 22.2 mmol/l glucose: 640 ± 120.1 vs. 1,615 ± 196.9 µg x µg [protein.sup.-1]. 30 [min.sup.-1] in normal vs. RIP-HGF islets, P < 0.01), have two- to threefold higher GLUT2 and glucokinase steady-state mRNA levels, take up and metabolize glucose more effectively, and most importantly, function at least twice as effectively after transplantation. These findings indicate that HGF has surprisingly positive effects on β-cell mitogenesis, glucose sensing, β-cell markers of differentiation, and transplant survival. It appears to have a unique and unanticipated effective profile as an islet mass- and function-enhancing agent in vivo., Recent clinical studies have documented that human islet transplantation has the potential to replace pancreatic endocrine function in patients with type 1 diabetes (1,2). However, the current shortage of human [...]

Published
2001

31. High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus

Author

Esteban, Juan Ignacio, Lopez-Talavera, Juan Carlos, Genesca, Juan, Madoz, Pedro, Viladomiu, Luis, Muniz, Eduardo, Martin-Vega, Carmen, Rosell, Manuel, Allende, Helena, Vidal, Xavier, Gonzalez, Antonio, Hernandez, Jose Manuel, Esteban, Rafael, and Guardia, Jaime

Subjects
Hepatitis C -- Demographic aspects, Hepatitis C virus, Blood donors -- Health aspects, Health
Abstract

Generally, the presence of antibodies against a virus in the blood of patients suggests previous exposure to that virus with immunity to it. Antibodies against hepatitis C virus (HCV), the major cause of transfusion-induced hepatitis, do not suggest immunity to HCV, but indicate ongoing infectivity. Only in recent months has a test been available to detect these antibodies, but because some research has suggested that only approximately 20 percent of HCV-positive donors will infect recipients, this test may not be cost-effective to perform on all donated blood. A study of over 30,000 blood donors was done to determine (retrospectively) the prevalence of HCV antibodies and the rate of hepatitis C transmission. A total of 368 donors were identified as HCV-positive, but only 254 were available for follow-up study. Factors found to be significant risks for HCV infection in the donors were having family members with chronic liver disease, a history of blood transfusion or major surgery, a history of hepatitis, a history of intravenous drug use or tattooing, and a history of acupuncture. None of the positive donors in the follow-up study had symptoms of liver disease at the time of donation or at follow-up. However, 9 percent had physical signs of liver disease, such as an enlarged liver. Nearly 40 percent of the donors had abnormal liver blood tests, and out of over 100 subjects who underwent liver biopsy, 84 percent had microscopic abnormalities. Evaluation of those donors for whom sufficient information was available to determine how infectious they were showed that 84 percent of the donors infected their recipients with HCV. This study demonstrates that HCV generally produces liver disease, at least on biopsy, and that it is more infectious than originally assumed. Potential blood donors identified as HCV-positive should be monitored carefully, as they may be at higher risk for liver disease than previously believed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

32. Efficacy of Ombitasvir/Paritaprevir/ and Dasabuvir +/-Ribavirin in Patients Receiving Concomitant Acid-Reducing Agents in Phase 3 Trials

Author

Shiffman, Mitchell, primary, Rustgi, Vinod, additional, Bennett, Michael, additional, Forns, Xavier, additional, Asselah, Tarik, additional, Vila, Ramon Planas, additional, Pedrosa, Marcos, additional, Neff, Guy, additional, DʼAmico, Ronald, additional, Ball, Greg, additional, Lopez-Talavera, Juan Carlos, additional, and Reau, Nancy, additional

Published
2015
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33. 1014 Improvement in Liver Function and Non-Invasive Estimates of Liver Fibrosis 48 Weeks After Treatment With Ombitasvir/Paritaprevir/R, Dasabuvir and Ribavirin in HCV Genotype 1 Patients With Cirrhosis

Author

Flamm, Steven L., primary, Morgan, Timothy R., additional, Fried, Michael W., additional, Poordad, Fred, additional, Wedemeyer, Heiner, additional, Berg, Thomas, additional, Foster, Graham, additional, Craxi, Antonio, additional, Larrey, Dominique, additional, Trinh, Roger, additional, Lovell, Sandra S., additional, Tang, Yuanyuan, additional, Pedrosa, Marcos, additional, Lopez-Talavera, Juan Carlos, additional, and Jacobson, Ira M., additional

Published
2015
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34. Islet Growth Factors

Author

Vasavada, Rupangi C., primary, Garcia-Ocaña, Adolfo, additional, Takane, Karen K., additional, Cebrian, Ana, additional, Lopez-Talavera, Juan Carlos, additional, and Stewart, Andrew F., additional

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37. Distribution and clinical correlates of viral and host genotypes in C hinese patients with chronic hepatitis C virus infection

Author

Rao, Huiying, primary, Wei, Lai, additional, Lopez‐Talavera, Juan Carlos, additional, Shang, Jia, additional, Chen, Hong, additional, Li, Jun, additional, Xie, Qing, additional, Gao, Zhiliang, additional, Wang, Lei, additional, Wei, Jia, additional, Jiang, Jianning, additional, Sun, Yongtao, additional, Yang, Ruifeng, additional, Li, Hong, additional, Zhang, Haiying, additional, Gong, Zuojiong, additional, Zhang, Lunli, additional, Zhao, Longfeng, additional, Dou, Xiaoguang, additional, Niu, Junqi, additional, You, Hong, additional, Chen, Zhi, additional, Ning, Qin, additional, Gong, Guozhong, additional, Wu, Shuhuan, additional, Ji, Wei, additional, Mao, Qing, additional, Tang, Hong, additional, Li, Shuchen, additional, Wei, Shaofeng, additional, Sun, Jian, additional, Jiang, Jiaji, additional, Lu, Lungen, additional, Jia, Jidong, additional, and Zhuang, Hui, additional

Published
2014
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38. Hepatocytes Undergo Phenotypic Transformation to Biliary Epithelium in Organoid Cultures

Author

Michalopoulos, George K., Bowen, William C., Mulè, Karen, Lopez-Talavera, Juan Carlos, and Mars, Wendy

Subjects
Male, Organ Culture Techniques, Phenotype, Staining and Labeling, Dipeptidyl Peptidase 4, Hepatocytes, Animals, Epithelial Cells, Biliary Tract, Article, Biomarkers, Rats, Inbred F344, Rats
Abstract

Organoid cultures of hepatocytes in the presence of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) display characteristic histologic organization. Biliary epithelium covers the surface of the tissue exposed to the culture medium. Hepatocytes, stellate cells and endothelial cells compose the underlying structures. In order to investigate the origin of the biliary epithelial cells in the organoid cultures, we utilized the retrorsine/DPPIV system of hepatocyte transplantation to create hybrid livers in which clones of DPPIV hepatocytes colonize variable portions of the lobules. We demonstrate that, as others have shown, biliary epithelium in this in vivo system remains that of the recipient (DPPIV negative) rat. Hepatocytes are the only cells positive for the DPPIV marker enzyme in the hybrid livers. Organoid cultures were prepared from the hybrid livers. Overall, 46.82% of the hepatocytes placed into culture were positive for DPPIV at time zero (after isolation). At 21 days in culture, 47.54% of the biliary epithelium on the surface of the organoid cultures was positive for DPPIV. Since the only DPPIV cells inoculated in the cultures were hepatocytes, this finding demonstrates that, in the conditions of the organoid cultures, hepatocytes do undergo phenotypic transition to biliary epithelial cells.

Published
2002

40. Single- and Multiple-Ascending-Dose Studies of the NS3 Protease Inhibitor Asunaprevir in Subjects with or without Chronic Hepatitis C

Author

Pasquinelli, Claudio, primary, McPhee, Fiona, additional, Eley, Timothy, additional, Villegas, Criselda, additional, Sandy, Katrina, additional, Sheridan, Pamela, additional, Persson, Anna, additional, Huang, Shu-Pang, additional, Hernandez, Dennis, additional, Sheaffer, Amy K., additional, Scola, Paul, additional, Marbury, Thomas, additional, Lawitz, Eric, additional, Goldwater, Ronald, additional, Rodriguez-Torres, Maribel, additional, DeMicco, Michael, additional, Wright, David, additional, Charlton, Michael, additional, Kraft, Walter K., additional, Lopez-Talavera, Juan-Carlos, additional, and Grasela, Dennis M., additional

Published
2012
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44. Interleukin-6, Nitric Oxide, and the Clinical and Hemodynamic Alterations of Patients With Liver Cirrhosis

Author

Genesca, Joan, primary, Gonzalez, Antonio, additional, Segura, Rosa, additional, Catalan, Robert, additional, Marti, Ramon, additional, Varela, Encarna, additional, Cadelina, Greg, additional, Martinez, Moises, additional, Lopez-Talavera, Juan Carlos, additional, Esteban, Rafael, additional, Groszmann, Roberto J, additional, and Guardia, Jaime, additional

Published
1999
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