Browsing by Author "Arrese, Marco"
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- Item805 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, OslandoBackground: 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.
- ItemA 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.
- ItemAn 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/.
- ItemAssessment 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.
- ItemBaveno 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.
- ItemCharacterization 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 EdgardoNonalcoholic 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.
- ItemChemical 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
- ItemCholecystectomy 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, FlavioBackground & 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.
- ItemCholic 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
- ItemEffect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis(WILEY, 2007) Ibanez, Patricio; Solis, Nancy; Pizarro, Margarita; Aguayo, Gloria; Duarte, Ignacio; Miquel, Juan Francisco; Accatino, Luigi; Arrese, MarcoBackground and aim: Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH.
- ItemEffects of Japanese herbal medicine inchin-ko-to on endotoxin-induced cholestasis in the rat(MEXICAN ASSOC HEPATOLOGY, 2009) Pablo Arab, Juan; Ramirez, Carolina; Munoz, Pablo; Pizarro, Margarita; Solis, Nancy; Riquelme, Arnoldo; Arrese, MarcoBackground/Objective. Inchin-ko-to (ICKT) is an herbal medicine used in Japan to treat jaundice and liver fibrosis. We investigated the effect of oral ICKT supplementation on endotoxin-induced cholestasis in the rat. Material and methods. Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used as a model of sepsis-induced cholestasis. Bite flow, biliary bile salt secretion, biliary glutathione secretion and protein expression of the main hepatobiliary transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by conventional techniques in ICKT treated and non-treated animals. Results. Injection of LIDS induced a significant decrease of bite ftow (-24%), biliary bite salts (-40%) and glutathione excretion (-70%) as well as a significant decrease in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially prevented the effects of LIPS determining a less intense reduction in bile flow (-10%), a normalization of glutathione excretion as well as a significant increase in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT administration did not modify the effects of LPS on BS secretion or Ntcp protein levels. Conclusion. Our data show that oral. supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bite salt-independent ftow.
- ItemEvaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia(2020) Rosa, L.; Muñoz Durango, Natalia; García Cañete, Patricia; Bizama, Carolina; González Briones, Ximena María; Wichmann Pérez, Ignacio Alberto; Arrese, Marco; Ferreccio Readi, Catterina; Kalergis Parra, Alexis Mikes; Miquel P., Juan Francisco; Roa Strauch, Juan Carlos Enrique; Lobos-Gonzalez, L.; Gomez, N.; Saavedra, N.; Guevara, F.; Villegas, J.; Espinoza, J. A.
- ItemExploring metabolic dysfunction-associated steatotic liver disease in lean individuals from Chile: Analysis of metabolic and genetic parametersAyala Valverde, María; Arrese, Marco; Pontificia Universidad Católica de Chile. Facultad de MedicinaIntroduction: Steatotic liver disease associated with metabolic dysfunction (MASLD) is the most common liver disease in the world. Obesity is the most relevant risk factor, but MASLD can also be observed in people with normal weight. Aim: This study aimed to analyze the features of MASLD in Chilean patients with normal body mass index (BMI) and particularly the frequency of the rs738409 risk polymorphism in Chilean individuals with hepatic steatosis. Methods: A cross-sectional study was conducted involving 181 randomly selected participants diagnosed with MASLD from the prospective Maule Cohort (MAUCO). Participants were categorized into lean, overweight, and obese groups based on their BMI. The presence of the rs738409 polymorphism was examined using Sanger sequencing. Statistical analyses of clinical data and genotypes encompassed Fisher's exact test, Chi-square test, Kruskal-Wallis test, and prevalence analysis. Results: 31.49% (57) were classified as thin, 36.3% (61) as overweight and 39.8% (67) as obese. Apart from higher ALT levels (p=0.004) and body fat percentage in obese subjects, no significant differences were found between the groups in terms of clinical characteristics or comorbidities. The allelic frequency of rs738409 was 77.1%, 83.6% and 82.5% in lean, overweight, and obese subjects, respectively, with no significant differences evident. Conclusions: In this sample of Chilean subjects with MASLD there were no significant differences linked to BMI with respect to the clinical characteristics of MASLD or the allele frequency of rs738409. Nevertheless, lean subjects with MASLD share cardiometabolic characteristics when compared to overweight and obese individuals.
- ItemExtracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy(2020) Hernández Villanueva, Alejandra Andrea; Arab Verdugo, Juan Pablo; Reyes, Daniela; Lapitz, Ainhoa; Moshage, Han; Bañales, Jesús M.; Arrese, MarcoIn recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic.
- ItemFarnesoid X Receptor Critically Determines the Fibrotic Response in Mice but Is Expressed to a Low Extent in Human Hepatic Stellate Cells and Periductal Myofibroblasts(ELSEVIER SCIENCE INC, 2009) Fickert, Peter; Fuchsbichler, Andrea; Moustafa, Tarek; Wagner, Martin; Zollner, Gernot; Halilbasic, Emina; Stoeger, Ulrike; Arrese, Marco; Pizarro, Margarita; Solis, Nancy; Carrasco, Gonzalo; Caligiuri, Alessandra; Sombetzki, Martina; Reisinger, Emil; Tsybrovskyy, Oleksiy; Zatloukal, Kurt; Denk, Helmut; Jaeschke, Hartmut; Pinzani, Massimo; Trauner, MichaelThe nuclear bile acid receptor, farnesoid X receptor (FXR), may play a pivotal role in liver fibrosis. We tested the impact of genetic FXR ablation in four different mouse models. Hepatic fibrosis was induced in wild-type and FXR knock-out mice (FXR-/-) by CCl4 intoxication, 3,5-diethoxycarbonyl-1,4-dihydrocollidine feeding, common bile duct ligation, or Schistosoma mansoni (S.m.)-infection. In addition, we determined nuclear receptor expression levels (FXR, pregnane X receptor (PXR), vitamin D receptor, constitutive androstane receptor (CAR), small heterodimer partner (SHP)) in mouse hepatic stellate cells (HSCs), portal myofibroblasts (MFBs), and human HSCs. Cell type-specific FXR protein expression was determined by immunohistochemistry in five mouse models and prototypic human fibrotic liver diseases. Expression of nuclear receptors was much lower in mouse and human HSCs/MFBs compared with total liver expression with the exception of vitamin D receptor. FXR protein was undetectable in mouse and human HSCs and MFBs. FXR loss had no effect in CCl4-intoxicated and S. m.-infected mice, but significantly decreased liver fibrosis of the bitiary type (common bile duct ligation, 3,5-diethoxycarbonyl-1,4-dihydrocoUidine). These data suggest that FXR loss significantly reduces fibrosis of the biliary type, but has no impact on non-cholestatic liver fibrosis. Since there is no FXR expression in HSCs and MFBs in liver fibrosis, our data indicate that these cells may not represent direct therapeutic targets for FXR ligands. (Am J Pathol 2009, 175;2392-2405; DOI: 10.2353/ajpath.2009.090114)
- ItemFragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena(2017) Arab Verdugo, Juan Pablo; Hernández Rocha, Cristián Antonio; Morales, Carolina; Vargas Domínguez, José Ignacio; Solis, Nancy; Pizarro Rojas, Margarita Alicia; Robles, Camila; Sandoval, Daniela; Ponthus, Simon; Benítez Gajardo, Carlos Esteban; Barrera Martínez, Francisco José; Soza, Alejandro; Riquelme Pérez, Arnoldo; Arrese, MarcoLa esteatohepatitis no alcohólica (EHNA) es la forma más agresiva de hígado graso no alcohólico (HGNA) e involucra el riesgo de progresión a etapas más avanzadas de enfermedad hepática. Se requieren métodos no invasivos para identificar a pacientes con EHNA. Objetivo: Evaluar el rendimiento diagnóstico de la determinación de los niveles séricos de citoqueratina-18 como marcador no invasivo de EHNA en población chilena. Métodos: Se determinaron los niveles séricos de CK-18 en un grupo de 41 pacientes con HGNA-probado por biopsia. El diagnóstico de EHNA se basó en los criterios histológicos recomendados (presencia de balonamiento) y se calculó el puntaje de actividad del HGNA (PAH) y grado de fibrosis. Mediante correlación de Spearman se evaluó la asociación entre CK-18 y PAH. Se confeccionó una curva ROC para evaluar la capacidad de CK-18 como test diagnóstico para EHNA. Además, se evaluó el rendimiento del puntaje de fibrosis en hígado graso no alcohólico (NFS) para pesquisa de fibrosis y EHNA y se lo comparó con CK-18 por regresión lineal simple. Los datos son expresados en medianas [percentil 25-75] y evaluados con test de rangos de Wilcoxon. Resultados: La edad promedio del grupo estudiado (23% hombres) fue de 50,4±11,1 años. Un 34,2% fue diagnosticado con EHNA (PAH≥5). Los niveles de CK-18 fueron mayores en los pacientes con EHNA versus los sin EHNA (183,6 UI/l [97,4-734,4] vs. 117,2 UI/l [83,8-954,8], p=0,016). Los niveles de CK-18 fueron buenos predictores de la presencia de EHNA en la biopsia con un área bajo la curva (AUC) de 0,732 (IC95% 0,572-0,897). Un punto de corte de 130,5 UI/l de CK-18 exhibió una sensibilidad de 92,9% y una especificidad de 63%, con un VPP de 56,5% y un VPN 94,4%, y clasificó correctamente al 73,2% de los pacientes con EHNA. El NFS tuvo un buen rendimiento para diagnóstico de fibrosis avanzada (AUC 0,739, IC95% 0,56–0,91), pero limitado para identificar EHNA (AUC 0,413, IC95% 0,21-0,61). Conclusión: La determinación de CK-18 es un buen marcador no invasivo de EHNA. Si bien, NFS tiene un buen rendimiento en la identificación de pacientes con fibrosis avanzada, no fue de utilidad para diagnosticar EHNA. En pacientes con HGNA, la determinación de CK-18 y NFS es útil en la pesquisa de EHNA y fibrosis hepática respectivamente.
- ItemInsulin resistance, hepatic steatosis and hepatitis C: A complex relationship with relevant clinical implications(ELSEVIER ESPANA, 2010) Arrese, Marco; Riquelme, Arnoldo; Soza, AlejandroInsulin resistance (IR) is a common pathophysiological condition where higher-than-normal concentrations of insulin are needed to maintain a normal glycemia and adequate glucose utilization in insulin target tissues. A high proportion (50-80%) of patients chronically infected with the hepatitis C virus (HCV) exhibit evidence of IR. Basic and clinical studies have disclosed a complex bidirectional relationship between IR and HCV infection that has important clinical implications. HCV infection may promote IR through direct viral-dependent mechanisms or due to activation of the inflammatory response resulting in increased production of Tumor Necrosis Factor-alpha and other cytokine-related molecules. These abnormalities may act synergistically with pre-existing metabolic risk factors and result in the development of hepatic steatosis and type 2 diabetes mellitus (T2DM) which are frequently found in the setting of HCV infection. Moreover, in addition to underlying metabolic abnormalities leading to its development hepatic steatosis also exhibit genotype-specific pathogenic mechanisms. A number of studies have shown that hepatic steatosis is associated to fibrosis progression in patients with HCV and that IR has a negative impact on the response rates to interferon-a-based therapy. Thus, modification of these factors through life-style changes or pharmacological agents may represent an undervalued specific target of therapy aiming to improve sustained virological response rates and reduce HCV related-morbidity and mortality.
- ItemIntrahepatic fatty acids composition as a biomarker of NAFLD progression from steatosis to NASH by using 1H-MRS(2019) Xavier, Aline Carvalho da Silva; Zacconi, Flavia C. M.; Gaínza Kunstmann, Constanza Mikela; Cabrera García, Daniel Alejandro; Arrese, Marco; Uribe Arancibia, Sergio A.; Sing-Long C., Carlos A.; Andía Kohnenkampf, Marcelo EdgardoNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world and it is becoming one of the most frequent cause of liver transplantation. Unfortunately, the only available method that can reliably determine the stage of this disease is liver biopsy, however, it is invasive and risky for patients. The purpose of this study is to investigate changes in the intracellular composition of the liver fatty acids during the progression of the NAFLD in a mouse model fed with Western diet, with the aim of identify non-invasive biomarkers of NAFLD progression based in H-1-MRS. Our results showed that the intracellular liver fatty acid composition changes as NAFLD progresses from simple steatosis to steatohepatitis (NASH). Using principal component analysis with a clustering method, it was possible to identify the three most relevant clinical groups: normal, steatosis and NASH by using H-1-MRS. These results showed a good agreement with the results obtained by GC-MS and histology. Our results suggest that it would be possible to detect the progression of simple steatosis to NASH using H-1-MRS, that has the potential to be used routinely in clinical application for screening high-risk patients.
- ItemLocalization of the Sodium-Taurocholate cotransporting polypeptide in membrane rafts and modulation of its activity by cholesterol in vitro(ELSEVIER SCIENCE BV, 2008) Molina, Hector; Azocar, Lorena; Ananthanarayanan, Meenakshisundaram; Arrese, Marco; Miquel, Juan FranciscoBackground: The relevance of discrete localization of hepatobiliary transporters in specific membrane microdomains is not well known. Aim: To determine whether the Na+/taurocholate cotransporting polypeptide (Ntcp), the main hepatic sinusoidal bile salt transporter, is localized in specific membrane microdomains. Methods: Presence of Ntcp in membrane rafts obtained from mouse liver was studied by immunoblotting and immunofluorescence. HEK-293 cells stably transfected with rat Ntcp were used for in vitro studies. Expression, localization and function of Ntcp in these cells were assessed by immunoblotting, immunofluorescence and biotinylation studies and Na+-dependent taurocholate uptake assays, respectively. The effect of cholesterol depletion/repletion assays on Ntcp function was also investigated. Results: Ntcp localized primarily to membrane rafts in in vivo studies and localized partially in membrane rafts in transfected HEK-293 cells. In these cells, membrane cholesterol depletion resulted in a shift of Ntcp localization into non-membrane rafts, which correlated with a 2.5-fold increase in taurocholate transport. Cholesterol repletion shifted back part of Ntcp into membrane rafts, and normalized taurocholate transport to values similar to control cells. Conclusion: Ntcp localizes in membrane rafts and its localization and function are regulated by membrane cholesterol content. This may serve as a novel regulatory mechanism of bile salt transport in liver. (C) 2008 Elsevier B.V. All rights reserved.
- ItemMild hypothermia does not affect liver regeneration after partial hepatectomy in mice(WILEY, 2009) Pablo Arab, Juan; Pizarro, Margarita; Solis, Nancy; Sun, Hongdan; Thevananther, Sundararajah; Arrese, MarcoThe use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration.
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