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Abstract Introduction The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. Methods We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. Results A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. Conclusions MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

Conflict of interest: Yes, FONDECYT #1241450 Introduction and Objectives: Although Latinos living in the United States are at higher risk of steatotic liver disease (SLD), information from Latin American countries is extremely scarce. We aimed to characterize SLD in Latin America and explore the role of the common genetic variants in this region. Patients / Materials and Methods: Cross-sectional multicenter study including individuals with SLD who undergo liver biopsy or transient elastography (TE) between 2003–2024. TE thresholds were established as follows: significant fibrosis (F2) ≥8.2 kPa, advanced fibrosis (F3) ≥9.7 kPa, and cirrhosis (F4) ≥13.6 kPa. Analyses included logistic binary regression. Results and Discussion: We included 2,159 patients (93.7% metabolic dysfunction-associated SLD and 6.3% alcohol-associated liver disease) from 13 centers in 5 countries (Argentina, Brazil, Chile, Mexico, and Peru). Mean age was 54.3±14.3 years old, 58.8% were female, and 60.2% had a liver biopsy. Around 18% had significant fibrosis, 18.7% advanced fibrosis, and 16.2% had cirrhosis. Additionally, 21.8% were homozygous carriers of the rs738409 risk polymorphism (PNPLA3 I148M variant), 42.5% were heterozygotes, and 35.7% were non-carriers. In an adjusted multivariable model, only age (odds ratio [OR]:1.03; 95%CI:1.01–1.04; p=0.030), body mass index (BMI) (OR:1.04; 95%CI:1.01–1.08, p=0.008), prediabetes/diabetes (OR:2.41; 95%CI:1.48–3.91, p

Conflict of interest: No Introduction and Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is linked to sarcopenia and exacerbated by obesity. Individuals with higher relative skeletal muscle mass are protected against MASLD or more likely to see its resolution, regardless of demographic and health-related factors. This study examines the effects of muscle mass enhancement, independent of exercise, on MASLD progression using myostatin knockout (Mstn-KO) mice, which are genetically modified to exhibit increased muscle mass due to myostatin deficiency. Patients / Materials and Methods: 11-week-old Mstn-KO mice and their wild-type counterparts were fed a Western diet (WD) for 24 weeks to induce MASLD. Parameters assessed included liver steatosis through histological analysis, muscle mass via MRI and histological cross-sectional area, exercise performance through treadmill tests, and muscle strength measured by electrophysiology. Results and Discussion: Mstn-KO mice showed significantly reduced liver steatosis (-20%) and increased muscle mass (+30%) compared to wild-type controls. Additionally, liver pro-inflammatory cytokines such as IL-1β and TNF-α were decreased in Mstn-KO mice, along with lower expression of lipogenesis-related genes, indicating a protective effect against MASLD progression. Histological assessments showed less hepatic lipid accumulation and inflammation in Mstn-KO mice, correlating with decreased myosteatosis and an enhanced cross-sectional area of muscle fibers. Muscle mass was measured by bioimpedance analysis, and paravertebral muscle area was evaluated using MRI. Electrophysiological measures indicated increased tetanic strength in Mstn-KO mice. Despite these physiological improvements, treadmill test results did not show significant differences in exercise performance between Mstn-KO and wild-type groups, suggesting that muscle mass improvement did not translate into enhanced exercise capacity. These results indicate that Mstn-KO mice are protected against muscle atrophy and MASLD progression. Conclusions: Our findings suggest that increased muscle mass, independent of exercise performance, can significantly ameliorate MASLD histology. Mstn-KO mice serve as a valuable model for exploring muscle-liver crosstalk in liver diseases, indicating potential treatment pathways that do not rely on exercise enhancement.

Conflict of interest: Yes, Fondecyt # 1241450 Introduction and Objectives: Background: There is limited information on features of lean MASLD patients in Latino subjects. We aimed to analyze the features of MASLD in Chilean patients with normal body mass index (BMI), the frequency of the rs738409 risk polymorphism (PNPLA3 I148M variant) and metabolomic profiles in Chilean individuals with MASLD. Patients / Materials and Methods: A cross-sectional study involving 181 randomly-selected participants diagnosed with MASLD from the prospective Maule Cohort (BMC Public Health. 2016;16:122). Participants were categorized into lean, overweight, and obese groups based on their BMI. The presence of the rs738409 polymorphism was examined using Sanger sequencing. Metabolomics was assessed using UHPLC-MS in a separate group of biopsy-proven MASLD patients. Statistical analyses of clinical data and genotypes encompassed Fisher's exact test, Chi-square test, Kruskal-Wallis test. Results and Discussion: 31.49% (57) were classified as thin, 36.3% (61) as overweight and 39.8% (67) as obese. Higher ALT levels (p=0.004) and body fat percentage in obese subjects were the only significant differences found among the groups. The allelic frequency of rs738409 was similar among groups 77.1%, 83.6% and 82.5% in lean, overweight, and obese subjects, respectively (n.s.). Circulating metabolome showed increased levels of ceramides in overweight and obese patients compared to lean subjects (p

Conflict of interest: No Introduction and Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is linked to sarcopenia, which worsens disease's prognosis. The complex liver-muscle crosstalk opens the possibility that improvements in muscle quantity and quality may be directly beneficial for MASLD. This study investigates the effects of s-pindolol, a beta-blocker known for its anabolic properties, on both muscle mass and function as well as on MASLD progression in mice. Patients / Materials and Methods: Male C57BL6 mice were subjected to a western diet (WD) for 20 weeks to induce MASLD and then mice were randomly grouped and treated with 3 mg/kg s-pindolol twice a week or left untreated. Assessments included grip and isolated muscle strength, body composition via bioimpedance spectroscopy, Abdominal MRI, liver histology, serum analyses and gene expression profiling. Results and Discussion: S-pindolol reduced liver steatosis and inflammation and was associated with lower levels of MCP-1, IL-10, TGF-β, and ACACA (Acetyl-CoA Carboxylase Alpha). S-pindolol also counteracted IGF-1 serum levels reduction seen in WD-fed mice. In addition, S-pindolol treatment led to an increase in muscle mass as confirmed by bioimpedance spectroscopy and MRI techniques. While exercise performance remained unchanged, grip strength improved together with a reduction in myosteatosis suggesting enhanced muscle quality. This was supported by an increase in muscle fiber diameter, indicating muscular hypertrophy independent of exercise. Conclusions: S-pindolol treatment ameliorates MASLD and enhances muscle quality in WD-fed mice. It may be hypothesized that s-pindolol's positive effects on muscle mass and function could play a role in its beneficial effects on MASLD through improvement of secretion of various salutary myokines. The present data underscore S-pindolol's therapeutic potential in MASLD.

Conflict of interest: No Introduction and Objectives: Liver fibrosis is an important prognostic factor in alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatohepatitis liver disease (MASLD). New drugs in steatotic liver disease (SLD), such as Resmetirom, are indicated in individuals with at least significant fibrosis. Cytokeratin-18 is a hepatocyte cytoskeleton protein that is released during apoptosis in its cleaved form by caspases (M30) and can be used as a non-invasive test (NIT) to stratify liver fibrosis. However, data on its performance is scarce in the Hispanic population. We aim to evaluate the diagnostic performance and additive value of M30 to identify significant fibrosis in a cohort of patients with ALD and MASLD. Patients / Materials and Methods: We conducted a cross-sectional cohort study of patients with ALD and MASLD who underwent liver biopsy or transient elastography between 2014–2023. The cutoff points for significant fibrosis (F2) and cirrhosis by transient elastography were ≥7.8 and ≥12.5 kPa, respectively. A receiver operator characteristic (ROC) was used to assess the performance of M30 and FIB-4. Results and Discussion: We included 55 ALD and 43 MASLD patients. The median age was 51 [42–60] years and 70.4% were male. Median liver stiffness was 6.8 [4.6–27.9] kPa and median M30 190.4 [146-274.8] U/l. Around 41.8% had F2 and 33.6% had cirrhosis. FIB-4 outperformed M30 in predicting significant fibrosis (AUROC 0.88 vs. 0.66, p-value=0.007) and cirrhosis (AUROC 0.93 vs. 0.56, p-value

Conflict of interest: No Introduction and Objectives: Inflammatory bowel disease (IBD) is a globally increasing condition. There is growing interest in the comorbidities associated with IBD, including steatotic liver disease (SLD). SLD has been demonstrated in individuals with IBD, even in the absence of other metabolic factors. Few studies have evaluated this association in the Latin American population. Objectives: The study aims to evaluate the frequency of SLD in Chilean subjects with IBD and its association with clinical and metabolic variables. Patients / Materials and Methods: We conducted a retrospective cross-sectional study of 148 adults with IBD (Crohn's disease: 89, ulcerative colitis: 46, and unclassified colitis: 13) who had abdominal imaging such as ultrasound, CT, or MRI in the last 15 years. Patients were considered to have SLD if this diagnosis was reported in the imaging report. Differences between groups were evaluated using chi-square and non-parametric tests. Results and Discussion: The median age of this cohort was 48 years (Q1: 37, Q3: 63 years), and 85 (57.4%) were female. Thirty patients (20.2%) had SLD. Subjects with SLD had significantly higher weight (75.8 vs 66kg, p

Metabolic Dysfunction-Associated Fatty Liver Disease and Diabetes Mellitus are two prevalent metabolic disorders that often coexist and synergistically contribute to the progression of each other. Several pathophysiological pathways are involved in the association, including insulin resistance, inflammation, and lipotoxicity, providing a foundation for understanding the complex interrelationships between these conditions. The presence of MASLD has a significant impact on diabetes risk and the development of microvascular and macrovascular complications, and diabetes significantly contributes to an increased risk of liver fibrosis progression in MASLD and the development of hepatocellular carcinoma. Moreover, both pathologies have a synergistic effect on cardiovascular events and mortality.Therapeutic interventions targeting MASLD and diabetes are discussed, considering lifestyle modifications, pharmacological agents, and emerging treatment modalities. The review also addresses the challenges in managing these comorbidities, such as the need for personalized approaches and the potential impact on cardiovascular health. The insights gleaned from this analysis can inform clinicians, researchers, and policymakers in developing integrated strategies for preventing, diagnosing, and managing these metabolic disorders.

Liver disease poses a substantial burden in Latin America. This burden is primarily attributed to a high level of alcohol consumption and the increasing prevalence of risk factors associated with metabolic dysfunction-associated steatotic liver disease (MASLD), such as sedentary lifestyles, easy access to ultra-processed foods, obesity, and type 2 diabetes mellitus. These epidemiological trends are cause for concern, especially considering that there are significant challenges in addressing them due to disparities in access to liver disease screening and care. In this article, we aim to provide an overview of the current situation regarding liver disease in Latin America. We also discuss recent multinational proposals designed to address the growing MASLD burden via its integration into existing non-communicable diseases policies, at both local and global levels. Additionally, we emphasize the urgent need to establish effective public health policies that target both MASLD risk factors and excessive alcohol consumption. Furthermore, we discuss the development of liver transplantation programs, areas for improvement in medical education and research capabilities, and how the fostering of extensive collaboration among all stakeholders is crucial for addressing liver disease in the region.

Introducción: Las enfermedades psiquiátricas constituyen un grupo de enfermedades con alta morbimortalidad que afectan a la calidad de vida. El riesgo cardiovascular (RCV) está aumentado en estas. Objetivo: Asociar enfermedades psiquiátricas con factores y RCV en personas con hipertensión arterial en la consulta ambulatoria de un hospital de salud mental. Método: Estudio observacional, en pacientes con hipertensión arterial y enfermedad psiquiátrica, ambulatorios, en hospital especializado en Quito (Ecuador) durante el año 2019. Se utilizaron medidas de tendencia central y pruebas de asociación, con IC95%. Resultados: Edad promedio 56.48 (± 13.51) años, predominan las mujeres, tendencia a obesidad (IMC 31.60 ± 5.51), hipertrigliceridemia (183.96 ± 97.63 mg/dl) y c-HDL disminuido (38.4 ± 18.53 mg/dl). Los diagnósticos psiquiátricos son el trastorno del humor (44.8%), trastornos orgánicos (26.7%), esquizofrenia (15.2%) y trastorno bipolar (13.3%). El 6% de los pacientes tienen RCV elevado, no significativo, los antipsicóticos no tuvieron impacto estadístico. Conclusiones: Es imperativa la evaluación y el tratamiento integral de pacientes con enfermedad psiquiátrica para disminuir el RCV aunque no puedan ser identificables con escalas de riesgo clásicas, por lo que se recomendaría otras tomando en cuenta particularidades del paciente, como uso de medicamentos y factores de riesgo adicionales.

Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) diagnosis requires a liver biopsy, which is inapplicable to large populations. Alternatively, NAFLD can be detected indirectly by non-invasive methods such as Fatty Liver Index (FLI) and Lipid Accumulation Product (LAP). Thus, the prevalence of NAFLD and its association with lifestyle habits (e.g., physical activity) can be studied within populations. This study aimed to (i) estimate the prevalence of NAFLD by FLI and LAP in the adult Chilean population and (ii) determine the association between the presence of NAFLD and physical activity levels. Materials and Methods: We analyzed the National Health Survey of Chile 2016-2017. Individuals meeting these criteria were included: 21-75 years old; absence of hepatitis B/C, HIV, acquired immunodeficiency syndrome, syphilis, chancre, and gonorrhea; alcohol consumption

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20–30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

BackgroundNon-alcoholic fatty liver disease is a liver condition that is increasing worldwide and expected to become the number one cause of cirrhosis and hepatocellular carcinoma in the next 5 years. Currently there are no successful or approved pharmacological treatments. Weight loss is the first-line therapy as a 7 to 10% reduction improves steatosis, inflammation, hepatocyte ballooning, and fibrosis. To achieve this, lifestyle interventions including daily exercise and diet must be encouraged. We aimed to assess the effects of diet, exercise, or a combination of both compared to conventional treatment in patients with non-alcoholic fatty liver disease.Methods and findingA literature search was performed in CENTRAL, EMBASE, and PubMed. Randomized controlled trials comparing lifestyle changes with conventional treatment were included, without date restriction. Two authors searched studies according to eligibility criteria, extracted data, and assessed study quality. Subgroup analysis was made by type of intervention, duration of intervention and supervision. We calculated mean differences between the intervention and the control group with their corresponding 95% confidence intervals. Quality of the evidence was assessed using the Cochrane Risk of bias tool. This study is registered in PROSPERO, number CRD42020184241, and checked with the PRISMA checklist. 30 RCTs met the inclusion criteria. Compared to conventional treatment, combined exercise with diet seems to elicit greater reductions in ALT (MD: -13.27 CI 95% -21.39, -5.16), AST (MD: -7.02 CI 95% -11.26, -2.78) and HOMA-IR (MD: -2.07 CI 95% -2.61, -1.46) than diet (ALT MD: -4.48 CI 95% -1.01, -0.21; HOMA-IR MD: -0.61 CI 95% -1.01, -0.21) and exercise (ALT and AST non-significant; HOMA-IR MD = -0.46 CI 95% -0.8, -0.12) alone. Additionally, exercise improved quality of life, cardiorespiratory fitness, and weight (MD: -2.64 CI 95% -5.18, -0.09).ConclusionLifestyle changes are effective in the treatment of NAFLD. Diet and exercise combined are superior to these interventions alone in improving liver enzymes and HOMA-IR.

HCV infection is associated with an increased incidence of cardiovascular (CV) events. Mechanisms underlying this association remain unknown. In our study, twenty HCV patients (median age 60.5 years, 65% male and 80% with cirrhosis) were evaluated prior, during and after direct-acting antiviral treatment. Ninety percent of patients achieved sustained virological response (SVR). Significant changes were observed in LDL particle size index, measured by LDL-C/apoB ratio, which increased after treatment (p = 0.023). In addition, HDL antioxidant capacity improved gradually from 34.4% at baseline to 42.4% at 4 weeks (p = 0.011), 65.9% at end of treatment EOT (p = 0.002) and remained elevated at 12-week (p = 0.001) after EOT compared to baseline values. Our findings suggest that a shift to a less atherogenic lipid profile may be a possible mechanism associated with CV risk reduction in patients with HCV infection achieving SVR.

Introduction and Objectives: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. Materials and Methods: C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. Results: Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p

Introduction and aim: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. Material and methods: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52 ± 14 years] who underwent 202 LT during the period 2003–2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor–recipient cohort. Youden index was calculated to identify optimal cutoff points. Results: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689–0.812), 0.702 (CI95% 0.634–0.764) and 0.610 (CI95% 0.539–0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score

Flutamide is a first-generation nonsteroidal antiandrogen, used for treatment of advanced prostate cancer (PCa). We present the clinical case of a patient with localized high-risk PCa who started flutamide before radical prostatectomy and evolved with acute liver failure and liver transplantation. Hepatotoxicity induced by antiandrogen therapy, and current indications for first generation anti-androgen therapy were reviewed. To our knowledge, this is the first report of a man diagnosed with PCa who evolved with acute liver failure secondary to flutamide, and finally required liver transplantation.

Background Peripheral artery disease (PAD) is associated with cardiovascular risk in type 2 diabetes mellitus (DM). The ankle-brachial index (ABI) is used for diagnosis of PAD. Objectives Establish the prevalence and incidence rate for PAD and determine the associated factors and survival time for the development of PAD. Methods Retrospective cross-sectional cohort study (follow up: 10 years) in 578 DM patients with at least 1 ABI measurement in a primary level of care diabetes clinic. Data was collected from clinical records. Sociodemographic and laboratory variables were analyzed determining its association (mean difference and bivariate logistic regression). Survival was calculated through life tables and Kaplan-Meier analysis. Results The prevalence of PAD was 13.98%. The incidence rate through the time of follow up was 23.38 per 1000 person-year (95% CI: 19.91-27.26). The group that developed PAD showed higher glycated hemoglobin levels ( P = .025), more years of DM ( P

Background: The success of primary health care relies on the integration of empowered practitioners with cooperative patients regardless of socioeconomic status. Using resources efficiently would help to improve healthcare promotion and reduce complications of chronic non-communicable diseases (NCDs). The importance of network support programmes relies on the fact that they allow to accurately deliver medical care by shaping a sense of community and purpose among the patients. Aim: To evaluate the effectiveness of a network support programme for patients with type 2 diabetes mellitus (T2DM). Design & setting: A centre-based observational prospective study took place in a primary care setting in Ecuador. Method: The impact of the diabetes care programme was assessed by comparing initial and final metabolic characteristics and outcomes of 593 patients with T2DM, followed-up from April 2007 to December 2017, using paired sample t-test. Electrocardiograms (ECGs), ankle-brachial indexes (ABIs), ocular fundus, and monofilament neuropathy tests were assessed with the McNemar test to evaluate complications at the beginning and end of the study. Results: Glycated haemoglobin (HbA1c), lipid profile, and systolic blood pressure (SBP) showed statistically significant decreases between the initial measurement (IMs) and final measurements (FMs). In the FM, significantly lower HbA1c, diastolic blood pressure (DBP), and atherogenic index were found. Despite the length of time since diagnosis, during the follow-up time, long-term micro- and macro-vascular complications, such as ocular fundus, serum creatinine, and ABI, remained unchanged throughout the period of active participation in this healthcare programme. Conclusion: This study demonstrates the feasibility of reducing plasma glucose, plasma lipids, and long-term complications in patients with T2DM by implementing a network support programme, which involves the medical team and patients themselves in an environment with limited resources.

Evaluation patients with nonalcoholic steatohepatitis (NASH) imply the need of appropriate assessment of disease severity (i.e. the presence of NASH) as well as of the disease stage (i.e. the extent of liver fibrosis). Liver biopsy (LB) is still considered the gold standard for diagnosing NASH as well as for establishing the degree of liver fibrosis. However, due to its invasive nature and costs, use of LB should be restricted to selected patients and, according guidelines and expert opinion, indicated in the following scenarios: a) when LB will guide treatment, b) to confirm or exclude NAFLD in patients with conflicting clinical data, c) to increase patient’s awareness about their disease, and improve engagement in their care and d) for inclusion in clinical trials. However, the role fo LB in NAFLD is evolving since when new and costly therapeutic agents become available, LB will be eventually necessary to make clinical decisions. The use of non-invasive tools (NITs) to assess steatosis, NASH and hepatic fibrosis is useful to triage NAFLD patients and decide in whom perform a LB.

The efficiency of conventional heating energy source compared with Infrared (IR), Ultrasound (US), Microwave and the simultaneous combination US–IR eco-friendly approaches for preparation of new N-(5-R1 -amino-2-nitrophenyl)acetamides and 5-R1-amino-2-nitroaniline by Nucleophilic Aromatic Substitution (SNAr) via addition–elimination reactions on the halogens F, Cl, Br, I, employing amines as nucleophiles were explored. Moreover, phenyldiazenyl derivatives in good yields by an oxidative one-pot SNAr-based amination reaction from an unusual oxidation of 2-phenylhydrazinyl derivatives in DMSO was prepared.

Abstract Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid–defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week). Also, we assessed serum levels of alanine-aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1β expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.

5-Fluorouracil (5-FU) is a chemotherapeutic agent frequently used for the treatment of solid tumors. In a few cases, 5-FU can be associated with coronary vasospasm, cardiac ischemia, or life-threatening arrhythmias. Recognition of 5-FU cardiotoxicity is clinically important as after the rapid sensation of therapy, cardiotoxicity can be completely reversible, and on the other hand, readministration may lead to serious damage of the heart and even death. A 70-year-old male came to the emergency department (ED) with chest pain which started while receiving an infusion of 5-FU. The patient did not have a personal history or risk factors of coronary artery disease and his electrocardiogram (ECG) before starting chemotherapy was completely normal. In the ED, his ECG had ischemic changes, troponin was elevated, and echocardiogram showed anterior wall hypokinesis. However, emergent coronary angiogram did not reveal any acute coronary occlusion. 5-FU-induced cardiotoxicity was suspected; the patient was admitted to a progressive care unit for close monitoring and infusion of calcium channel blockers was initiated. The patient’s symptoms and ECG findings gradually resolved, and two days later on discharge, patient was chest pain free and ECG was normal. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, describes its clinical course, and emphasizes the importance of better awareness and early recognition of the rare side effect as it may allow physicians to reduce the risk of life-threatening complications.

Severe untreated hypothyroidism has been shown to affect cardiovascular function. While there have been a few reports of life-threatening arrhythmias occurring as a direct result of the hypothyroid state, very few cases of cardiac arrest have been reported in the literature. We report one such case of a middle-aged man who suffered a cardiac arrest that was attributed to severe untreated hypothyroidism. Keywords: Myxedema coma, Hypothyroidism, Cardiac arrest, Prolonged QTc

The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to myc-ophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. Aim. To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients.Material and methods. 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range).Results. 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m2 and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis.Conclusion. A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.

Initiation of insulin therapy can be challenging for patients; proper training should be given by physicians and certified educators to ensure correct and safe use for outpatient population. Different insulin strengths are now available in the US; while U-40 insulin does not exist in the United States for humans, it is a very common strength used in animals. We are reporting a 30-year-old male that became insulin dependent after hospitalization for necrotizing pancreatitis who was using U-40 syringes to draw from the prescribed insulin U-100 and also presented with repeated hypoglycemic episodes.

Background and rationale for the study. FGF19/15 is a gut-derived hormone presumably governing bile acid (BA) synthesis and gallbladder (GB) refilling. FGF19 mRNA is present in human GB cholangiocytes (hGBECs); however, the physiological significance of GB-derived FGF19 remains unknown. We investigated whether hGBECs secrete FGF19 and the effects of cholecystectomy on serum FGF19 ([FGF19]s) and BA synthesis.Material and methods. FGF19 expression was assessed by qRT-PCRs and immunostaining in hGBECs and terminal ileum, and quantified in bile and serum by ELISA. Basal and BA (chenodexycholic acid, CDCA) induced FGF19 expression and secretion was analyzed in primary cultured hGBECs and GB-d1 cell line. Pre and postprandial serum changes in [FGF19]s, 7α-hydroxy-4-cholestene-3-one (C4, a marker of BA synthesis) and BA were evaluated in plasma of gallstone disease patients at baseline and after cholecystectomy.Results. FGF19 mRNA levels were -250-fold higher in hGBECs compared to distal ileum. GB bile contained -23-fold higher FGF19 levels compared to serum (p < 0.0001). CDCA induced dose-dependent expression and secretion of FGF19 in hGBECs and GB-d1 cells. Cholecystectomy increased plasma BA synthesis ≥ 2-fold (p < 0.0001), and altered the diurnal rhythm and significantly reduced [FGF19]s noon peak. BA serum levels, serum cholesterol and triglyceride content remained unchanged.Conclusions. In conclusion human GB cholangiocytes constitutively express and secrete high levels of FGF19 in a process regulated by BA. Resection of this organ doubles BA synthesis concomitantly with changes in [FGF19]s. These findings suggest a potential connection between GB cholangiocytes-derived FGF19 and BA metabolism that could lead to metabolic dysregulation following cholecystectomy.

The first generation protease inhibitors has been the mainstay of hepatitis C treatment for the last couple of years, showing marked improvement in sustained virological response, but also increased side effects. Infection has emerged as a common complication of telaprevir and boceprevir in combination with peginterferon and ribavirin, usually caused by common pathogens. We present the case of a 65 years old man who developed a Mycobacterium abscessus pulmonary infection during treatment with telaprevir, peginterferon and ribavirin. The patient was successfully treated with amikacin, imipenem and chlarithro-mycin. The present case is relevant for increasing awareness for recognition of opportunistic infections and particularly nontuberculous mycobacterial infections in patients receiving triple therapy for chronic hepatitis C, especially in cirrhotic subjects who develop significant lymphopenia.

Resumen INTRODUCCIÓN El flumazenil es un antagonista del complejo receptor GABA/benzodiacepinas que podría tener un rol en el manejo de la encefalopatía hepática. Sin embargo, existe controversia sobre su eficacia y seguridad. MÉTODOS Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos dos revisiones sistemáticas que en conjunto incluyen catorce estudios aleatorizados. Concluimos que el uso de flumazenil no disminuye la mortalidad en pacientes con encefalopatía hepática, y no está claro si produce alguna mejoría clínica porque la certeza de la evidencia es muy baja.

The recent discovery of bile acid (BA) receptors and a better delineation of the multiple roles of BAs in relevant biological processes have revamped BA research. The vasoactive actions of BAs were recognized more than three decades ago but the underlying mechanisms of the BA-induced vasorelaxation are now being clarified. Recent evidence shows that the BA receptors FXR and TGR5 are expressed in endothelial cells and may have important effects on both systemic and portal circulation. The availability of genetically engineered mice with ablation of BA receptors and the development of BA receptor agonists has allowed to explore the modulation of FXR and, in a lesser extent, of TGR5 in the setting of portal hypertension (PHT) with promising results. In this review, we summarize recent data on how BA-dependent pathways influence several processes that impact in PHT and the preclinical data showing that pharmacological modulation of those pathways may hold promise in the treatment of PHT.

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Introducción. La acumulación de grasa visceral se asocia al desarrollo de enfermedad hepática. La elastografía hepática es un método novedoso no invasivo para evaluar fibrosis hepática. Objetivo. Evaluar la relación entre el volumen de tejido adiposo visceral (VAT), volumen de tejido adiposo subcutáneo (SAT) medido por resonancia magnética (RM), con índices de elastografía hepática (EH) utilizando ARFI (fuerza de impulso de radiación acústica) en pacientes con Diabetes Mellitus tipo 2 (DM2). Métodos. Fueron incluidos 20 pacientes (edad promedio: 62 años, rango: 55-75 años, peso promedio: 77,8 kg, rango: 61,5-97 kg) con DM2. Los pacientes se sometieron a un examen de RM en un resonador Philips Intera 1.5T. Al protocolo de RM se agregó una secuencia de excitación espectral centrada en el peak de grasa. La secuencia incluyó 32 cortes transversales, grosor 7mm, desde la cúpula diafragmática hasta el borde inferior renal. En las imágenes se midió VAT utilizando el software Image J (freeware). En cada paciente se realizó una EH, utilizando ARFI con 10 medidas en lóbulo hepático derecho. Finalmente, se realizó un análisis estadístico a través de la correlación de Pearson entre los volúmenes de grasa abdominal y ARFI. Resultados. El promedio de VAT fue 2472 ± 861 cc, (1173-4020 cc), el promedio de ARFI fue 1,62 ± 0,8 m/s, (0,8-3,4 m/s). Se obtuvieron correlaciones de r=-0,08 entre VAT y ARFI (p=0,72), de 0,13 entre SAT y ARFI (p=0,57), y de -0,06 entre (VAT+SAT) con ARFI (p=0,77). Subdividiendo el universo muestral, se encontró que el grupo con ARFI mayor que 1,6 m/s (7 pacientes) obtuvo una correlación de 0,63 entre VAT y ARFI (p=0,12), de 0,66 entre SAT y ARFI (p=0,10), y de 0,94 entre (VAT+SAT) con ARFI (p=0,001). En el subgrupo con ARFI inferior a 1,6 m/s (13 pacientes) la correlación fue 0,11 entre VAT y ARFI (p=0,71), de 0,26 entre SAT y ARFI (p=0,38), y de 0,32 entre (VAT+SAT) y ARFI (p=0,28). Al ajustar por género en el subgrupo de mujeres con ARFI mayor que 1,6 m/s (6 pacientes), se encontró que la correlación de ARFI y VAT fue de 0,79 (p=0,05), y de 0,92 (p=0,009) para VAT+SAT. Conclusiones. En los pacientes DM2 con índices ARFI superior a 1,6 m/s habría una buena correlación con VAT y VAT+ SAT, indicando que aquellos con mayor daño hepático tendrían más acumulación de grasa abdominal.Background. Increase in visceral fat is associated to the development of fatty liver and liver fibrosis. Hepatic elastography is a novel noninvasive method for assessing liver fibrosis. Objective. To evaluate the relationship between visceral adipose tissue volume (VAT), subcutaneous adipose tissue volume (SAT) as measured by Magnetic Resonance Imaging (MRI) and transient elastography (TrE) values using ARFI (Acoustic Radiation Force Impulse) in type 2 Diabetic Mellitus patients (DM2). Methods. We included 20 DM2 patients (mean age: 62 years, range: 55-75, mean weight: 77.8 kg, range: 61.5-97). Patients underwent an MRI study in a Philips Intera 1.5T scanner. MR imaging protocol included a spectral excitation sequence centered on the fat peak. The sequence included 32 cross sections, 7mm thick, from the diaphragmatic cupula to the inferior border of the kidney. VAT was measured by using the semiautomatic Image J software. Each patient underwent a hepatic elastograpy (HE); 10 ARFI measurements were performed in the right hepatic lobe. Finally, a statistical analysis was performed by applying Pearson correlation between abdominal fat volumes and ARFI scores Results. Mean VAT was 2472 ± 861 cc, (1173-4020 cc), whilst the mean ARFI was 1.62 ± 0.8 m/s, (0.8-3.4 m/s). Correlations obtained were r=0.08 between VAT and ARFI (p=0.72); 0.13 between SAT and ARFI (p=0.57), and -0.06 between (VAT+SAT) and ARFI (p=0.77). By subdividing the sample universe, we observed that the group with ARFI scores greater than 1.6 m/s (7 patients) had a correlation of 0.63 between VAT and ARFI (p=0.12); of 0.66 between SAT and ARFI (p=0.10), and of 0.94 between VAT+SAT and ARFI (p=0.001). In the subgroup with ARFI values inferior to 1.6 m/s (13 patients), the correlation was of 0.11 between VAT and ARFI (p=0.71); of 0.26 between SAT and ARFI (p=0.38), and of 0.32 between ( VAT+SAT) and ARFI (p=0.28). When adjusted for gender, ARFI scores greater than 1.6m/s (6 patients) in the subgroup of female patients revealed a correlation of 0.79 (p=0.05) between ARFI and VAT, and of 0.92 (p=0.009) for VAT+SAT. Conclusions. In DM2 patients, ARFI values greater than 1.6 m/s seem to be indicative of a good correlation between VAT and VAT+SAT, thus indicating that those with greater liver damage may present increased abdominal fat accumulation.

Background and objective. Prophylaxis therapy is indicated in cirrhotic patients with large esophageal varices or small varices with red wale signs (high risk esophageal varices; HREV). Endoscopic surveillance to detect HREV is currently recommended. The objective of this study is to identify non-invasive predictors of HREV in cirrhotic patients.Design and methods. Adult cirrhotic patients without previous variceal bleeding were prospectively included. All patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio (PC/SD) was calculated for all patients. The association of these variables with the presence of HREV in upper endoscopy was tested using univariate and multivariate analysis. Receiver operating characteristic (ROC) curves were constructed for variables associated with HREV.Results. Sixty-seven patients were included. The prevalence rate of HREV was 50%. Age, gender (female), platelet count, spleen diameter, PC/ SD ratio, total bilirrubin, prothrombin activity (INR), Child-Pugh score, clinical and ultrasonographic ascites were significantly associated with presence of HREV in univariate analysis. Age and PC/SD ratio were the parameters independently associated with HREV in a multivariate analysis, with OR 8.81 (CI 95%: 1.7-44.9) and OR 11.21 (CI 95%: 2.8-44.6) respectively. A PC/SD ratio cut-off value under 830.8 predicted HREV with 76.9% sensitivity, 74.2% specificity and 77.8% negative predictive value (ROC curve area: 0.78).Conclusions. The PC/SD ratio was significantly associated with HREV, but with suboptimal sensitivity and specificity. Therefore, the results of this study do not support the routine clinical use of PC/SD ratio for screening of HREV.

Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as potential biomarkers for clinically significant and advanced fibrosis.Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy.Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p

BackgroundChronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and findingsEnglish and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) ConclusionThe presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.

Introducción. La acumulación de grasa visceral se asocia al desarrollo de enfermedad hepática. La elastografía hepática es un método novedoso no invasivo para evaluar fibrosis hepática. Objetivo. Evaluar la relación entre el volumen de tejido adiposo visceral (VAT), volumen de tejido adiposo subcutáneo (SAT) medido por resonancia magnética (RM), con índices de elastografía hepática (EH) utilizando ARFI (fuerza de impulso de radiación acústica) en pacientes con Diabetes Mellitus tipo 2 (DM2). Métodos. Fueron incluidos 20 pacientes (edad promedio: 62 años, rango: 55-75 años, peso promedio: 77,8 kg, rango: 61,5-97 kg) con DM2. Los pacientes se sometieron a un examen de RM en un resonador Philips Intera 1.5T. Al protocolo de RM se agregó una secuencia de excitación espectral centrada en el peak de grasa. La secuencia incluyó 32 cortes transversales, grosor 7mm, desde la cúpula diafragmática hasta el borde inferior renal. En las imágenes se midió VAT utilizando el software Image J (freeware). En cada paciente se realizó una EH, utilizando ARFI con 10 medidas en lóbulo hepático derecho. Finalmente, se realizó un análisis estadístico a través de la correlación de Pearson entre los volúmenes de grasa abdominal y ARFI. Resultados. El promedio de VAT fue 2472 ± 861 cc, (1173-4020 cc), el promedio de ARFI fue 1,62 ± 0,8 m/s, (0,8-3,4 m/s). Se obtuvieron correlaciones de r=-0,08 entre VAT y ARFI (p=0,72), de 0,13 entre SAT y ARFI (p=0,57), y de -0,06 entre (VAT+SAT) con ARFI (p=0,77). Subdividiendo el universo muestral, se encontró que el grupo con ARFI mayor que 1,6 m/s (7 pacientes) obtuvo una correlación de 0,63 entre VAT y ARFI (p=0,12), de 0,66 entre SAT y ARFI (p=0,10), y de 0,94 entre (VAT+SAT) con ARFI (p=0,001). En el subgrupo con ARFI inferior a 1,6 m/s (13 pacientes) la correlación fue 0,11 entre VAT y ARFI (p=0,71), de 0,26 entre SAT y ARFI (p=0,38), y de 0,32 entre (VAT+SAT) y ARFI (p=0,28). Al ajustar por género en el subgrupo de mujeres con ARFI mayor que 1,6 m/s (6 pacientes), se encontró que la correlación de ARFI y VAT fue de 0,79 (p=0,05), y de 0,92 (p=0,009) para VAT+SAT. Conclusiones. En los pacientes DM2 con índices ARFI superior a 1,6 m/s habría una buena correlación con VAT y VAT+ SAT, indicando que aquellos con mayor daño hepático tendrían más acumulación de grasa abdominal.