Browsing by Author "Arrese, Marco"

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    805 Complications of Gastrointestinal Endoscopy in 85,391 Procedures
    (Mosby-Elsevier, 2012) Espino Espino, Alberto Antonio; García Astorquiza, Ximena Andrea; Mac Namara, Macarena; Richter Roca, Hugo Michael; Pimentel Muller, Fernando; Biel Morales, Francisco Javier; Robles García, Camila Fernanda; Callejas, Matías F.; Sharp Pittet, Allan Carlos; Donoso, Andrés; Candia Balboa, Roberto Andrés; González Donoso, Robinson; Jarufe Cassis, Nicolás; Arrese, Marco; Álvarez Lobos, Manuel; Padilla Pérez, Oslando
    Background: Complications are inherent to GI endoscopy (GIE) and do not necessarily imply endoscopist's negligence. They may occur even using highest standards of practice. Objectives: To analyze the frequency and severity of complications occurring within 30 days after of the GIE at a single university hospital in Chile. Methods: We reviewed the records about patients who underwent GIE from January 2001 through May 2011. Results: A total of 85,391 GIE were evaluated. Procedures: 46,928 (55%) esophagogastroduodenoscopy (EGD); 27,993 (32.8%) diagnostic colonoscopies; 1427 (1.7%) polypectomies; and other procedures (hemostasis, variceal band ligation (VBL), foreign-body removal, dilation, stents, PEG, ERCP, EUS and double balloon endoscopy) 9043 (10.5%). A total of 299 complications were associated with GIE (59 % female, mean age 63 years, range 5 - 99). The overall complications rate was 0.35% (cardiopulmonary (CP) 0.1%, bleeding 0.07%, perforation 0.06%, infection 0.04%, pancreatitis 0.03% and other). The overall complication rate was higher in therapeutic procedures (TP) vs diagnostic procedures (DP) (2.7% v/s 0.16%, p<0.0001). The percentage of severe complications was higher in TP vs DP (52.3% vs 28.4%, p<0.0001). The overall complication rate for EGD was 0.14% (CP 0.07%, perforation 0.017%, bleeding 0.019%); diagnostic colonoscopy, 0.27% (CP 0.1%, perforation 0.06%, bleeding 0.02%); and polypectomy, 1.8% (CP 0.14%, perforation 0.28%, bleeding 0.98%). A total of 15 deaths occurred (overall rate 0.018%, 83% in TP). The overall mortality rate was higher in TP vs DP (0.2% v/s 0.003%, p<0.0001). The mortality rate for PEG was 0.7%; VBL 0.4%; ERCP 0.2%; diagnostic colonoscopy 0.004%; EGD 0.004%; and polypectomy 0%. Conclusions: GIE is associated with complications and mortality. The severity and risk of complications are higher in therapeutic procedures. These risks should be clearly explained to patients and their family before the procedure.
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    A global action agenda for turning the tide on fatty liver disease
    (2024) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Anstee, Quentin M.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Gastaldelli, Amalia; Hagstrom, Hannes; Huang, Terry T. K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Terrault, Norah A.; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Joern M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care.Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance.Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
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    A global research priority agenda to advance public health responses to fatty liver disease
    (2023) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Hagstrom, Hannes; Huang, Terry T. -K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Miller, Veronica; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Jorn M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background & aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.
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    A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease
    (2022) Younossi, Zobair M.; Ong, Janus P.; Takahashi, Hirokazu; Yilmaz, Yusuf; Hi, Yuichiro Eguc; El Kassas, Mohamed; Buti, Maria; Diago, Moises; Zheng, Ming-Hua; Fan, Jian-Gao; Yu, Ming-Lung; Wong, Vincent Wai-Sun; Alswat, Khalid; Chan, Wah-Kheong; Mendez-Sanchez, Nahum; Burra, Patrizia; Bugianesi, Elisabetta; Duseja, Ajay K.; George, Jacob; Papatheodoridis, George, V; Saeed, Hamid; Castera, Laurent; Arrese, Marco; Kugelmas, Marcelo; Romero-Gomez, Manuel; Alqahtani, Saleh; Ziayee, Mariam; Lam, Brian; Younossi, Issah; Racila, Andrei; Henry, Linda; Stepanova, Maria
    BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally.
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    A Mineralocorticoid Receptor Deficiency in Myeloid Cells Reduces Liver Steatosis by Impairing Activation of CD8+ T Cells in a Nonalcoholic Steatohepatitis Mouse Model
    (2020) Munoz-Durango, Natalia; Arrese, Marco; Hernandez, Alejandra; Jara, Evelyn; Kalergis, Alexis M.; Cabrera, Daniel
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Arab, Juan Pablo; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Narro, Graciela E. Castro; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Howdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookbian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steato-hepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/ wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.(c) 2023 American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Fundacion Clinica Medica Sur, A.C. Published by Wolters Kluwer/Elsevier B.V/ Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Pablo Arab, Juan; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Castro Narro, Graciela E.; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Kowdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookoian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
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    A new definition for metabolic dysfunction-associated fatty liver disease : An international expert consensus statement
    (2020) Eslam, M.; Newsome, P. N.; Sarin, S. K.; Anstee, Q. M.; Targher, G.; Romero Gomez, M.; Zelber Sagi, S.; Wong, V. W. S.; Dufour, J. F.; Arrese, Marco; Schattenberg, J. M.; Kawaguchi, T.; Valenti, L.; Shiha, G.; Tiribelli, C.; Yki Jarvinen, H.; Fan, J. G.; Gronbaek, H.; Yilmaz, Y.; Cortez Pinto, H.; Oliveira, C. P.; Bedossa, P.; Adams, L. A.; Zheng, M. H.; Fouad, Y.; Chan, W. K.; Mendez Sanchez, N.; Ahn, S. H.; Castera, L.; Bugianesi, E.; Ratziu, V.; George, J.
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    Ability of a Combined FIB4/miRNA181a Score to Predict Significant Liver Fibrosis in NAFLD Patients
    (2021) Lima, Rodrigo Vieira Costa; Stefano, Jose Tadeu; Malta, Fernanda de Mello; Pinho, Joao Renato Rebello; Carrilho, Flair Jose; Arrese, Marco; Oliveira, Claudia P.
    Liver biopsy is the gold standard for assessing fibrosis, but there is a need to seek non-invasive biomarkers for this purpose. The aim of this study was to evaluate the correlation between the serum levels of the microRNAs miR-21, miR-29a, miR-122, miR-155 and miR-181a and the phenotypic expression of NAFLD. A cross-sectional study was carried out on 108 NAFLD patients diagnosed by liver biopsy. FIB-4 and NAFLD fibrosis scores were calculated. The comparison between the distributions of microRNA values according to the presence or absence of histological fibrosis (F2-F4) was performed. A multivariate logistic regression analysis was performed to build a score for predicting fibrosis using FIB-4 and Ln (miR-181a) as independent variables. Only miR-181a showed a statistical difference between patients with significant liver fibrosis (>F2) and those without (F0-F1) (p = 0.017). FIB-4 revealed an AUC on the ROC curve of 0.667 to predict clinically significant fibrosis (F2-F4). When assessed using the score in association with Ln (miR-181a), there was an improvement in the ROC curve, with an AUC of 0.71. miR-181a can be used as a non-invasive method of predicting fibrosis in NAFLD, and an association with FIB-4 has the potential to increase the accuracy of each method alone.
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    An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study
    (2024) Dunn, Winston; Li, Yanming; Singal, Ashwani K.; Simonetto, Douglas A.; Díaz Piga, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Ayares, Gustavo; Arnold Alvaréz, Jorge Ignacio; Ayala-Valverde, Maria; Perez, Diego; Gomez, Jaime; Escarate, Rodrigo; Fuentes López, Eduardo; Ramirez-Cadiz, Carolina; Morales-Arraez, Dalia; Zhang, Wei; Qian, Steve; Ahn, Joseph C.; Buryska, Seth; Mehta, Heer; Dunn, Nicholas; Waleed, Muhammad; Stefanescu, Horia; Bumbu, Andreea; Horhat, Adelina; Attar, Bashar; Agrawal, Rohit; Cabezas, Joaquin; Echavaria, Victor; Cuyas, Berta; Poca, Maria; Soriano, German; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Higuera-de-la-Tijera, Fatima; Kulkarni, Anand V.; Rao, P. Nagaraja; Guerra-Salazar, Patricia; Skladany, Lubomir; Kubanek, Natalia; Prado, Veronica; Clemente-Sanchez, Ana; Rincon, Diego; Haider, Tehseen; Chacko, Kristina R.; Romero, Gustavo A.; Pollarsky, Florencia D.; Restrepo, Juan C.; Toro, Luis G.; Yaquich, Pamela; Mendizabal, Manuel; Garrido, Maria L.; Marciano, Sebastian; Dirchwolf, Melisa; Vargas, Victor; Jimenez, Cesar; Hudson, David; Garcia-Tsao, Guadalupe; Ortiz, Guillermo; Abraldes, Juan G.; Kamath, Patrick S.; Arrese, Marco; Shah, Vijay H.; Bataller, Ramon; Arab, Juan P.
    Background and Aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. Approach and Results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores (p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. Conclusions: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/.
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    Assessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy
    (2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.
    Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
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    Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans
    (2023) Ayoub, Alan; Anugwom, Chimaobi M.; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Groothuismink, Zwier M. A.; Oliveira, Jeffrey; Boonstra, Andre; Debes, Jose D.
    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48-1.52, p = 0.58) and 0.81 (CI: 0.34-1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease.
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    Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans
    (2024) Fu, Siyu; Karim, Dhamina; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Oliveira, Jeffrey; Debes, Jose D.; Boonstra, Andre
    Introduction and Objectives: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. Materials and Methods: Cross-sectional analysis performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). Results: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). Conclusions: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC develop-ment in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.(c) 2023 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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    Baveno VI and Expanded Baveno VI criteria successfully predicts the absence of high-risk gastro-oesophageal varices in a Chilean cohort
    (2020) Gaete Celis, María Isabel; Díaz Piga, Luis Antonio; Arenas Fajardo, Cristian Alexis; Gonzalez, K.; Cattaneo, M.; Soza, Alejandro; Arrese, Marco; Barrera Martínez, Francisco José; Arab Verdugo, Juan Pablo; Benítez, Carlos; Fuster, F.; Henriquez, R.
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    Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers
    (2022) Abrigo, Johanna; Olguin, Hugo; Gutierrez, Danae; Tacchi, Franco; Arrese, Marco; Cabrera, Daniel; Valero-Breton, Mayalen; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, Claudio
    Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5(-/-) mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5(-/-) mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.
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    Changing epidemiology of hepatocellular carcinoma in South America: A report from the South American liver research network
    (2023) Farah, Marina; Anugwom, Chimaobi; Ferrer, Javier Diaz; Baca, Estefania Liza; Mattos, Angelo Z.; Possebon, Joao Pedro P.; Arrese, Marco; Prieto, Jhon; Balderramo, Domingo; Carrera, Enrique; Debes, Jose D.
    Introduction and objectives: Most epidemiological data on hepatocellular carcinoma (HCC) originate from resource-rich countries. We have previously described the epidemiology of HCC in South America through the South American Liver Research Network. Here, we provide an update on the changing epidemiology of HCC in the continent seven years since that report.Materials and methods: We evaluated all cases of HCC diagnosed between 2019 to 2021 in centers from six countries in South America. A templated, retrospective chart review of patient characteristics at the time of HCC diagnosis, including basic demographic, clinical and laboratory data, was completed. Diagnosis of HCC was made radiologically or histologically for all cases via institutional standards.Results: Centers contributed to a total of 339 HCC cases. Peru accounted for 37% (n=125) of patients; Brazil 16% (n=57); Chile 15% (n=51); Colombia 14% (n=48); Argentina 9% (n=29); and Ecuador 9% (n=29). The median age at HCC diagnosis was 67 years (IQR 59-73) and 61% were male. The most common risk factor was nonalcoholic fatty liver disease (NAFLD, 37%), followed by hepatitis C (17%), alcohol use disorder (11%) and hepatitis B (12%). The majority of HCCs occurred in the setting of cirrhosis (80%). HBV-related HCC occurred at a younger age compared to other causes, with a median age of 46 years (IQR 36-64).Conclusion: We report dramatic changes in the epidemiology of HCC in South America over the last decade, with a substantial increase in NAFLD-related HCC. HBV-related HCC still occurs at a much younger age when compared to other causes.(c) 2022 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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    Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS−/− mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
    (2023) Lavin, Begoña; Eykyn, Thomas; Phinikaridou, Alkystis; Xavier, Aline; Kumar, Shravan; Buqué, Xabier; Aspichueta, Patricia; Sing-Long C., Carlos A.; Arrese, Marco; Botnar, René Michael; Andía Kohnenkampf, Marcelo Edgardo
    Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS−/− mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS−/− mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3−/− mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS−/− murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.
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    Chemical hypoxia induces pro-inflammatory signals in fat-laden hepatocytes and contributes to cellular crosstalk with Kupffer cells through extracellular vesicles
    (2020) Hernández Villanueva, Alejandra Andrea; Geng, Y.; Sepúlveda, R.; Solis López, Nancy de las Mercedes; Torres, J.; Arab Verdugo, Juan Pablo; Barrera Martínez, Francisco Javier; Cabrera, D.; Moshage, H.; Arrese, Marco
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    Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice
    (WILEY, 2011) Amigo, Ludwig; Husche, Constanze; Zanlungo, Silvana; Luetjohann, Dieter; Arrese, Marco; Miquel, Juan F.; Rigotti, Attilio; Nervi, Flavio
    Background & aims: Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism. Methods: Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined. Results: BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P < 0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P < 0.03) and 50% (P < 0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P < 0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice. Conclusions: XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver.
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    Cholic acid and deoxycholic acid induce skeletal muscle atrophy through a mechanism dependent on TGR5 receptor
    (2020) Abrigo, J.; Gonzalez, F.; Aguirre, F.; Tacchi, F.; Gonzalez, A.; Meza, M. P.; Simon, F.; Cabrera García, Daniel Alejandro; Arrese, Marco; Karpen, S.; Cabello Verrugio, Claudio Alejandro