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Aim: To compare the performance of multi-echo chemical-shift-encoded (MECSE) magnetic resonance imaging (MRI) proton density fat fraction (PDFF) estimation, considering three different fat frequency peak combinations, for the quantification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD).Materials and Methods: The present study was a prospective cross-sectional research of 121 patients with metabolic syndrome and evidence of hepatic steatosis on ultrasound, who underwent a 3 T MRI examination. All patients were studied with a multifrequency MECSE sequence. The PDFF was calculated using six peaks (MECSEp123456), three peaks (MECSEp456), and a single peak (MECSEp5) model. The two simpler fat peak models were compared to the six peaks model, which was considered the reference standard. Linearity was evaluated using linear regression while agreement was described using Bland-Altman analysis.Results: The mean age was 47 (±9) years and BMI was 29.9 (±2.9) kg/m2. Steatosis distribution was 15%/31%/54% (S1/S2/S3, respectively). Compared to MECSEp123456, both models provided linear PDFF measurements (R2= 0.99 and 0.97, MECSEp456 and MECSEp5 respectively). Regression slope (0.92; p<0.001) and mean Bland-Altman bias (-1.5%; 95% limits of agreement: -3.19%, 0.22%) indicated minimal underestimation by using PDFF-MECSEp456. Nonetheless, mean differences in PDFF estimations varied from -1.5% (MECSEp456,p=0.006) to -2.2% (MECSEp5,p<0.001) when compared to full six fat frequencies model.Conclusion: Although simpler spectral fat MECSE analysis shows a linear relationship with the standard six peaks model, their variation in estimated PDFF values introduces a low but clinically significant bias in fat quantification and steatosis grading in NAFLD patients. [ABSTRACT FROM AUTHOR]

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background and Aims: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described., Approach and Results: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18])., Conclusions: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background and Aims: Alcohol use disorder has been reported in patients undergoing bariatric procedures, but the pattern of alcohol consumption has not been evaluated. We investigated the prevalence, risk factors, and impact of binge drinking (BD) at the time of surgery and during follow-up., Methods: A prospective, longitudinal study of subjects undergoing bariatric surgery was included in the LABS-2 registry between 2006 and 2009. Participants with AUDIT questionnaire at the time of surgery and a minimum of 12 months follow-up were included. BD was defined as consuming ≥5 drinks on at least 1 occasion in the previous month. Liver biopsies were obtained during bariatric procedures in not all cases. Survival analysis was performed with the adjusted Cox regression model and competing risk., Results: A total of 2257 subjects were included, with a median follow-up of 79 months. The prevalence of BD at time of surgery was 12%, and it raised up to 23% during follow-up. Patients with BD predominantly had a binge eating disorder (OR=1.35 [95% CI: 1.04-1.76]), regularly consumed fast food [OR=1.4 (95% CI: 1.07-1.85)] and used other drugs (OR=2.65 [95% CI: 1.74-4.04]). Within liver biopsies evaluation, BD showed higher hepatic iron deposits (OR=3.00 [95% CI: 1.25-7.21]). BD at the time of surgery was associated with a higher risk of BD during follow-up (OR=10.49 [95% CI: 7.86-14.00]) and long-term mortality (HR: 3.21 [95% CI: 1.67-6.18]). Specific causes of death in these patients with BD were liver disease (p=0.020), suicide (p=0.015), neoplasms (p=0.034), and respiratory (p=0.025)., Conclusions: The prevalence of BD in patients undergoing bariatric surgery is high and increases the risk of postoperative liver disease, suicides, and long-term mortality., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.

Introduction: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse., Objectives: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence., Methods: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence., Results: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01)., Conclusion: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity.

Background Standardized manual region of interest (ROI) sampling strategies for hepatic MRI steatosis and iron quantification are time consuming, with variable results. Purpose To evaluate the performance of automatic MRI whole-liver segmentation (WLS) for proton density fat fraction (PDFF) and iron estimation (transverse relaxometry [R2*]) versus manual ROI, with liver biopsy as the reference standard. Materials and Methods This prospective, cross-sectional, multicenter study recruited participants with chronic liver disease who underwent liver biopsy and chemical shift-encoded 3.0-T MRI between January 2017 and January 2021. Biopsy evaluation included histologic grading and digital pathology. MRI liver sampling strategies included manual ROI (two observers) and automatic whole-liver (deep learning algorithm) segmentation for PDFF- and R2*-derived measurements. Agreements between segmentation methods were measured using intraclass correlation coefficients (ICCs), and biases were evaluated using Bland-Altman analyses. Linear regression analyses were performed to determine the correlation between measurements and digital pathology. Results A total of 165 participants were included (mean age ± standard deviation, 55 years ± 12; 96 women; 101 of 165 participants [61%] with nonalcoholic fatty liver disease). Agreements between mean measurements were excellent, with ICCs of 0.98 for both PDFF and R2*. The median bias was 0.5% (interquartile range, -0.4% to 1.2%) for PDFF and 2.7 sec -1 (interquartile range, 0.2-5.3 sec -1 ) for R2* (P < .001 for both). Margins of error were lower for WLS than ROI-derived parameters (-0.03% for PDFF and -0.3 sec -1 for R2*). ROI and WLS showed similar performance for steatosis (ROI AUC, 0.96; WLS AUC, 0.97; P = .53) and iron overload (ROI AUC, 0.85; WLS AUC, 0.83; P = .09). Correlations with digital pathology were high ( P < .001) between the fat ratio and PDFF (ROI r = 0.89; WLS r = 0.90) and moderate ( P < .001) between the iron ratio and R2* (ROI r = 0.65; WLS r = 0.64). Conclusion Proton density fat fraction and transverse relaxometry measurements derived from MRI automatic whole-liver segmentation (WLS) were accurate for steatosis and iron grading in chronic liver disease and correlated with digital pathology. Automated WLS estimations were higher, with a lower margin of error than manual region of interest estimations. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moura Cunha and Fowler in this issue.

Background and Aims: Patients with decompensated cirrhosis frequently require hospital admissions, which are associated with worse prognosis. The aim of this study was to analyze the effect of TIPS on the need for hospital care. Secondary objectives were to assess the clinical and biological impact of TIPS and to identify predictors of post-TIPS hospital care., Methods: An observational, retrospective study of patients with decompensated cirrhosis treated with TIPS from January 2008 until March 2019. Exclusion criteria were TIPS placed for non-cirrhotic portal hypertension (PH) and patients referred from another hospital without prior or subsequent follow-up at our Unit. Hospital care, PH-related complications, and laboratory data were compared before and after TIPS., Results: The final cohort comprised 104 patients (72% male) with a mean age of 60 (± 10) years. Follow-up from first decompensation until TIPS and that from procedure to study completion were 7 (4.2-9.8) and 20 (4.6-35.4) months, respectively. TIPS was indicated mainly for refractory ascites (50%) and variceal bleeding (39%). Hemodynamic and clinical success rates were 97% and 92%, respectively. The number of emergency department visits and hospital admissions decreased after the procedure (p < 0.001). Improvement was seen in MELD and Child-Pugh scores, renal function, hyponatremia, and anemia after TIPS. Variceal bleeding as the indication for TIPS (OR 0.047; 95 CI 0.006-0,39; p < 0.05) together with early creation of the shunt (stage 3 vs 5; p < 0.05) were associated with a reduction in risk of post-TIPS hospital care., Conclusion: TIPS is a safe and effective procedure that reduces hospital care burden by improving PH-related complications, hepatic, renal function, hyponatremia, and anemia. Variceal bleeding as the indication and early placement of the device were associated with a reduction in post-TIPS hospital care. These findings support a role for this treatment, predominantly in the early stages of cirrhosis., (© 2021. Società Italiana di Medicina Interna (SIMI).)

Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessing different neurological functions: PHES (Psychometric Hepatic Encephalopathy Score) battery, d2, Stroop, Oral SDMT (Symbol Digit Modalities Test), Digit Span, number-letter test, and bimanual and visual-motor coordination tests. NAFLD patients show impairment in attention, mental concentration, psychomotor speed, cognitive flexibility, inhibitory mental control, and working memory. We developed a new, rapid, and sensitive score based on the most affected parameters in NAFLD patients, unveiling that 32% of NAFLD show MCI. Prevalence was similar in NAFL (36%) or NASH (27%) patients, but lower in NAFLD than in cirrhosis (65%). MCI prevalence is significant in NAFLD patients. Psychometric testing is warranted in these patients to unveil MCI and take appropriate measures to reverse and prevent its progression.

Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at high risk for 5-ASA non-response and appropriate therapeutic escalation are essential to avoid disease progression. However, the absence of a standardized definition for treatment success makes this a challenging task. The focus of the current review was to describe the risk factors and management strategies associated with 5-ASA non-response. Rates of 5-ASA failure can vary from 17 % to 75 % according to different success definitions, of which clinical relapse is the most prevalent and studied condition. Younger age and endoscopic activity at diagnosis, extensive colitis, early need for corticosteroids, elevated inflammatory markers and non-adherence are consistent risk factors of 5-ASA failure. Given the effectiveness, safety profile and tolerability of this medication, therapy optimization is critical before treatment escalation. Combined use of systemic and topical therapy at an appropriate dose in a once-daily administration and control of adherence could improve success rates.

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems., (Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)