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Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma.
Öcal, O, Ingrisch, M, Ümütlü, MR, Peynircioglu, B, Loewe, C, van Delden, O, Vandecaveye, V, Gebauer, B, Zech, CJ, Sengel, C, et al
British journal of cancer. 2022;(2):211-218
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Abstract
AIMS: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.
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Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss-weight maintenance.
Li, L, Spranger, L, Stobäus, N, Beer, F, Decker, AM, Wernicke, C, Brachs, S, Brachs, M, Spranger, J, Mai, K
Nutrition & diabetes. 2021;(1):31
Abstract
BACKGROUND/OBJECTIVES Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. SUBJECTS/METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points. RESULTS Circulating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5-4.9) vs. 3.8 (3.2-4.6) µg/ml; p = 2.1 × 10-5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = -0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B. CONCLUSIONS Our data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629 , date of registration: February 25, 2009.
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Eucaloric diets enriched in palm olein, cocoa butter, and soybean oil did not differentially affect liver fat concentration in healthy participants: a 16-week randomized controlled trial.
Stonehouse, W, Sergi, D, Benassi-Evans, B, James-Martin, G, Johnson, N, Thompson, CH, Abeywardena, M
The American journal of clinical nutrition. 2021;(2):324-337
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Abstract
BACKGROUND Effects of dietary fat quality on liver fat remain to be elucidated. Inconsistent evidence may be influenced by fatty acid saturation, chain-length, and regio-specificity within triacylglycerol (TAG) molecules. OBJECTIVES We aimed to compare eucaloric diets enriched in palm olein (POo), cocoa butter (COB), and soybean oil (SBO) on liver fat concentration in healthy participants. Secondary outcomes included visceral (VAT) and abdominal subcutaneous (aSCAT) adipose tissue, plus other obesity and cardiometabolic health outcomes. METHODS Eighty-three healthy participants (20-45 y, BMI 18.5-27.5 kg/m2) commenced and 64 completed a 16-wk randomized parallel intervention, preceded by a 2-wk run-in. Participants consumed identical eucaloric background diets differing in test fats [contributing 20% total energy intake (%E)], providing 33%E total fat with the following ratios for PUFAs/SFAs/MUFAs: POo, 4.2/13.5/15%E; SBO, 14.4/8.8/9.4%E; COB, 2.3/19.5/11%E. Liver fat and abdominal adiposity were measured at weeks 0 and 16 using 1H-magnetic resonance spectroscopy/imaging; all other outcomes were measured at 0, 4, 8, 12, and 16 wk. RESULTS Fat quality did not affect liver fat concentration, VAT, aSCAT, obesity indexes, blood pressure, liver enzymes, leptin, or fasting glucose. Body fat mass decreased with SBO and COB compared with POo. SBO decreased serum total cholesterol (TC), LDL cholesterol, and TC:HDL cholesterol relative to POo [estimated marginal mean (95% CI) differences: -0.57 (-0.94, -0.20) mmol/L; -0.37 (-0.68, -0.07) mmol/L; and -0.42 (-0.73, -0.11) mmol/L, respectively]. No diet differences were observed on HDL cholesterol, TAG, apoA1, apoB, apoB:apoA1, or fecal free fatty acids (FFAs), except for lower FFA pentadecanoic acid (15:0) with COB than with SBO and POo. CONCLUSIONS In healthy adults, when consumed as part of eucaloric typical Australian diets, 3 different dietary fat sources did not differentially affect liver fat concentration and amounts of adipose tissue. Effects on serum lipids were inconsistent across lipid profiles. The findings must be confirmed in metabolically impaired individuals before recommendations can be made.
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Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets.
Kabisch, S, Markova, M, Hornemann, S, Sucher, S, Pivovarova-Ramich, O, Machann, J, Hierholzer, J, Rohn, S, Pfeiffer, AFH
Scientific reports. 2021;(1):8843
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731-0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required.Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.
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Effect of cranberry supplementation on liver enzymes and cardiometabolic risk factors in patients with NAFLD: a randomized clinical trial.
Masnadi Shirazi, K, Shirinpour, E, Masnadi Shirazi, A, Nikniaz, Z
BMC complementary medicine and therapies. 2021;(1):283
Abstract
BACKGROUND We aimed to evaluate the effect of cranberry supplementation on serum liver enzymes, hepatic steatosis, and cardiometabolic risk factors in patients with non-alcoholic fatty liver (NAFLD). METHODS In the present parallel-designed randomized controlled clinical trial, 110 patients with NAFLD were enrolled. The patients were randomized to receive 144 mg cranberry capsule or placebo for 6 months. The primary efficacy of the treatment was lipid profile, glycemic measurements, and liver enzyme levels. RESULTS The data were reported for 46 in the supplementation group and 48 in the placebo group. The patient's mean (SD) age was 43.16 (11.08) years. No significant differences between groups were observed regarding the post-intervention level of liver enzyme. The mean after-intervention levels of total cholesterol (p < 0.001) and triglyceride (p = 0.01) were significantly lower in the intervention group compared with the placebo group. At the end of the study, the mean insulin and HOMA-IR levels were significantly lower in the cranberry group compared with the placebo group. Significantly more patients in the cranberry group experienced a decrease in steatosis level compared with the control group. CONCLUSION The results of the present study showed that cranberry supplementation had a positive effect on some lipid profiles, insulin resistance, and hepatic steatosis in patients with NAFLD. TRIAL REGISTRATION IRCT20200725048200N1 ; first registration date: 11.8.2020.
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Two methods for assessment of choline status in a randomized crossover study with varying dietary choline intake in people: isotope dilution MS of plasma and in vivo single-voxel magnetic resonance spectroscopy of liver.
Horita, DA, Hwang, S, Stegall, JM, Friday, WB, Kirchner, DR, Zeisel, SH
The American journal of clinical nutrition. 2021;(6):1670-1678
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BACKGROUND Choline deficiency has numerous negative health consequences; although the preponderance of the US population consumes less than the recommended Adequate Intake (AI), clinical assessment of choline status is difficult. Further, several pathways involved in primary metabolism of choline are estrogen-sensitive and the AI for premenopausal women is lower than that for men. OBJECTIVES We sought to determine whether in vivo magnetic resonance spectroscopy (MRS) of liver and/or isotope-dilution MS of plasma could identify biomarkers reflective of choline intake (preregistered primary outcomes 1 and 2, secondary outcome 1). Determination of whether biomarker concentrations showed sex dependence was a post hoc outcome. This substudy is a component of a larger project to identify a clinically useful biomarker panel for assessment of choline status. METHODS In a double-blind, randomized, crossover trial, people consumed 3 diets, representative of ∼100%, ∼50%, and ∼25% of the choline AI, for 2-wk periods. We measured the concentrations of choline and several metabolites using 1H single-voxel MRS of liver in vivo and using 2H-labeled isotope dilution MS of several choline metabolites in extracted plasma. RESULTS Plasma concentrations of 2H9-choline, unlabeled betaine, and 2H9-betaine, and the isotopic enrichment ratio (IER) of betaine showed highly significant between-diet effects (q < 0.0001), with unlabeled betaine concentration decreasing 32% from highest to lowest choline intake. Phosphatidylcholine IER was marginally significant (q = 0.03). Unlabeled phosphatidylcholine plasma concentrations did not show between-diet effects (q = 0.34). 2H9 (trimethyl)-phosphatidylcholine plasma concentrations (q = 0.07) and MRS-measured total soluble choline species liver concentrations (q = 0.07) showed evidence of between-diet effects but this was not statistically significant. CONCLUSIONS Although MRS is a more direct measure of choline status, variable spectral quality limited interpretation. MS analysis of plasma showed clear correlation of plasma betaine concentration, but not plasma phosphatidylcholine concentration, with dietary choline intake. Plasma betaine concentrations also correlate with sex status (premenopausal women, postmenopausal women, men).This trial was registered at clinicaltrials.gov as NCT03726671.
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Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial.
Goss, AM, Dowla, S, Pendergrass, M, Ashraf, A, Bolding, M, Morrison, S, Amerson, A, Soleymani, T, Gower, B
Pediatric obesity. 2020;(7):e12630
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common form of liver disease among adolescents in industrialized countries. While lifestyle intervention remains the hallmark treatment for NAFLD, the most effective dietary strategy to reverse NAFLD in children is unknown. OBJECTIVE The objective of this study was to determine the effects of a moderately CHO-restricted diet (CRD) vs fat-restricted diet (FRD) in adolescents with NAFLD on reduction in liver fat and insulin resistance. METHODS Thirty-two children/adolescents (age 9-17) with obesity and NAFLD were randomized to a CRD (<25:25:>50% energy from CHO:protein:fat) or FRD (55:25:20) for 8 weeks. Caloric intakes were calculated to be weight maintaining. Change in hepatic lipid content was measured via magnetic resonance imaging, body composition via dual energy X ray absorptiometry and insulin resistance via a fasting blood sample. RESULTS Change in hepatic lipid did not differ with diet, but declined significantly (-6.0 ± 4.7%, P < .001 only within the CRD group. We found significantly greater decreases in insulin resistance (HOMA-IR, <.05), abdominal fat mass (P < .01) and body fat mass (P < .01) in response to the CRD vs FRD. CONCLUSION These findings suggest that consumption of a moderately CHO-restricted diet may result in decreased hepatic lipid as well as improvements in body composition and insulin resistance in adolescents with NAFLD even in the absence of intentional caloric restriction. Larger studies are needed to determine whether a CHO-restricted diet induces change in hepatic lipid independent of change in body fat.
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Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol but does not affect liver fat and other cardiometabolic risk factors in healthy adults: the ATTIS study, a randomized controlled trial.
Dikariyanto, V, Smith, L, Francis, L, Robertson, M, Kusaslan, E, O'Callaghan-Latham, M, Palanche, C, D'Annibale, M, Christodoulou, D, Basty, N, et al
The American journal of clinical nutrition. 2020;(6):1178-1189
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BACKGROUND There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined. OBJECTIVES We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease (CVD). METHODS The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point. RESULTS Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference -0.25 mmol/L; 95% CI: -0.45, -0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation. CONCLUSIONS Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.
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Effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in obstructive jaundice: A randomized controlled trial.
Kakaei, F, Fasihi, M, Hashemzadeh, S, Zarrintan, S, Beheshtirouy, S, Asvadi-Kermani, T, Tarvirdizadeh, K, Rezaei, S, Sanei, B
Asian journal of surgery. 2020;(1):322-329
Abstract
BACKGROUND It has been shown that N-acetylcysteine may be useful in correcting postoperative hepatic and renal function in many pathological conditions. The present study aimed to examine the effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in patients with obstructive jaundice. METHODS & Materials: A total of 30 patients with obstructive jaundice who were candidates for bypass surgery were enrolled in this randomized clinical trial. In the case group, intravenous N-acetylcysteine (200 mg/kg per hour in the first 8 h, followed by 100 mg/kg per hour for another 16 h, the same dose for another 24 h) was administered postoperatively. Liver and renal function tests (serum AST, ALT, ALP, GGT, bilirubin, and creatinine) were compared between two groups, as well as duration of hospitalization and ICU stay. RESULTS Postoperatively, decrease in mean serum AST (p = 0.01), ALT (p = 0.02), ALP (p = 0.01), GGT (p = 0.04) and bilirubin (total, p = 0.02, direct, p = 0.01) levels compared to the preoperative values was significantly more among cases compared to those in controls. Changes in serum creatinine, however, did not differ significantly between two groups (p = 0.18). Hospital and ICU stays were also not different between two study groups (p = 0.27 and p = 0.94 respectively). CONCLUSION On the basis of our findings, intravenous N-acetylcysteine in patients with obstructive jaundice could significantly preserve liver function after bypass surgery. Effect of this medication on renal function; however, was not statistically significant. TRIAL REGISTRATION Iranian Registry of Clinical Trial: IRCT2016041016473N7.
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Effect of High-Intensity Interval Training on Visceral and Liver Fat in Cardiac Rehabilitation: A Randomized Controlled Trial.
Taylor, JL, Holland, DJ, Mielke, GI, Bailey, TG, Johnson, NA, Leveritt, MD, Gomersall, SR, Rowlands, AV, Coombes, JS, Keating, SE
Obesity (Silver Spring, Md.). 2020;(7):1245-1253
Abstract
OBJECTIVE This study aimed to investigate the effect of exercise intensity on visceral adipose tissue (VAT) and liver fat reduction in patients with coronary artery disease (CAD) over 3 months and the maintenance of improvements over 12 months. METHODS Forty-two participants with CAD were randomized to three sessions/week of either 4 × 4-minute high-intensity interval training (HIIT) or 40 minutes of usual care moderate-intensity continuous training (MICT) for a 4-week supervised cardiac rehabilitation program, followed by three home-based sessions/week for 11 months. Liver fat (as intrahepatic lipid) and VAT were measured via magnetic resonance techniques. Data are mean change (95% CI). RESULTS HIIT and MICT significantly reduced VAT over 3 months (-350 [-548 to -153] cm3 vs. -456 [-634 to -278] cm3 ; time × group effect: P = 0.421), with further improvement over 12 months (-545 [-818 to -271] cm3 vs. -521 [-784 to -258] cm3 ; time × group effect: P = 0.577) and no differences between groups. Both groups improved liver fat over 3 months, with HIIT tending to show greater reduction than MICT (-2.8% [-4.0% to -1.6%] vs. -1.4% [-2.4% to -0.4%]; time × group effect: P = 0.077). After 12 months, improvements were maintained to a similar degree. Higher exercise intensity predicted liver fat reduction (β = -0.3 [-0.7 to 0.0]; P = 0.042). CONCLUSIONS HIIT and MICT reduced VAT over 3 and 12 months. For liver fat, HIIT tended to provide a slightly greater reduction compared with MICT. These findings support HIIT as a beneficial adjunct or alternative to MICT for reducing visceral and liver fat in patients with CAD.