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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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Abstract
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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Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy.
Yoshizumi, T, Mori, M
Surgery today. 2020;(1):21-29
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Abstract
Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.
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Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn.
Hansen, TWR, Wong, RJ, Stevenson, DK
Physiological reviews. 2020;(3):1291-1346
Abstract
Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.
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Benefits and harms of ginseng supplementation on liver function? A systematic review and meta-analysis.
Ghavami, A, Ziaei, R, Foshati, S, Hojati Kermani, MA, Zare, M, Amani, R
Complementary therapies in clinical practice. 2020;:101173
Abstract
OBJECTIVE Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults. METHODS A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis. RESULTS Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals. CONCLUSION Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.
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Metabolic adaptations after bariatric surgery: adipokines, myokines and hepatokines.
Faramia, J, Ostinelli, G, Drolet-Labelle, V, Picard, F, Tchernof, A
Current opinion in pharmacology. 2020;:67-74
Abstract
This review addresses the impact of bariatric surgery on the endocrine aspects of white adipose tissue, muscle and the liver. We describe literature supporting the notion that adipokines, myokines and hepatokines likely act in concert and drive many of the long-term metabolic improvements following surgery. Circulating adiponectin is increased while secretion of pro-inflammatory interleukins (1, 6 and 8) decreases, alongside leptin secretion. The metabolic improvements observed in the muscle might relate to reduction of myokines contributing to insulin resistance (including myostatin, brain-derived neurotrophic factor and fibroblast growth factor-21). Subject to exception, hepatokine secretion is generally increased (such as insulin-like growth factor-binding protein 2, adropin and sex hormone-binding globulin). In conclusion, bariatric surgery restores metabolic functions by enhancing the time-dependent secretion of anti-inflammatory, insulin-sensitizing and antilipemic factors. Further research is needed to understand the molecular mechanisms by which these factors may trigger the remission of obesity-related comorbidities following bariatric surgery.
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Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker.
Baselli, GA, Dongiovanni, P, Rametta, R, Meroni, M, Pelusi, S, Maggioni, M, Badiali, S, Pingitore, P, Maurotti, S, Montalcini, T, et al
Gut. 2020;(10):1855-1866
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OBJECTIVE Efforts to manage non-alcoholic fatty liver disease (NAFLD) are limited by the incomplete understanding of the pathogenic mechanisms and the absence of accurate non-invasive biomarkers. The aim of this study was to identify novel NAFLD therapeutic targets andbiomarkers by conducting liver transcriptomic analysis in patients stratified by the presence of the PNPLA3 I148M genetic risk variant. DESIGN We sequenced the hepatic transcriptome of 125 obese individuals. 'Severe NAFLD' was defined as the presence of steatohepatitis, NAFLD activity score ≥4 or fibrosis stage ≥2. The circulating levels of the most upregulated transcript, interleukin-32 (IL32), were measured by ELISA. RESULTS Carriage of the PNPLA3 I148M variant correlated with the two major components of hepatic transcriptome variability and broadly influenced gene expression. In patients with severe NAFLD, there was an upregulation of inflammatory and lipid metabolism pathways. IL32 was the most robustly upregulated gene in the severe NAFLD group (adjusted p=1×10-6), and its expression correlated with steatosis severity, both in I148M variant carriers and non-carriers. In 77 severely obese, and in a replication cohort of 160 individuals evaluated at the hepatology service, circulating IL32 levels were associated with both NAFLD and severe NAFLD independently of aminotransferases (p<0.01 for both). A linear combination of IL32-ALT-AST showed a better performance than ALT-AST alone in NAFLD diagnosis (area under the curve=0.92 vs 0.81, p=5×10-5). CONCLUSION Hepatic IL32 is overexpressed in NAFLD, correlates with hepatic fat and liver damage, and is detectable in the circulation, where it is independently associated with the presence and severity of NAFLD.
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The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations.
Franco, V, Gershkovich, P, Perucca, E, Bialer, M
Clinical pharmacokinetics. 2020;(12):1493-1500
Abstract
For highly lipophilic drugs, passage into the intestinal lymphatic system rather than the portal vein following oral administration may represent a major alternative route of delivery into the general circulation. Increasing intestinal lymphatic transport provides an effective strategy to improve oral bioavailability when hepatic first-pass metabolism is a major rate-limiting step hampering access to the systemic circulation after oral dosing. The transfer of orally administered, highly lipid-soluble drugs to the lymphatic system is mediated by their association with chylomicrons, large intestinal lipoproteins that are assembled in the enterocytes in the presence of long-chain triglycerides or long-chain fatty acids. Due to its very high lipophilicity, cannabidiol (CBD) has physicochemical features (e.g. logP = 6.3) consistent with an oral absorption mediated at least in part by transport via the intestinal lymphatic system. CBD also undergoes extensive first-pass hepatic metabolism. Formulation changes favoring diversion of orally absorbed CBD from the portal to the lymphatic circulation pathway can result in reduced first-pass liver metabolism, enhanced oral bioavailability, and reduced intra- and intersubject variability in systemic exposure. In this manuscript, we discuss (1) evidence for CBD undergoing hepatic first-pass liver metabolism and lymphatic absorption to a clinically important extent; (2) the potential interplay between improved oral absorption, diversion of orally absorbed drug to the lymphatic system, and magnitude of presystemic elimination in the liver; and (3) strategies by which innovative chemical and/or pharmaceutical delivery systems of CBD with improved bioavailability could be developed.
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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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Effects of green tea or green tea catechin on liver enzymes in healthy individuals and people with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.
Mahmoodi, M, Hosseini, R, Kazemi, A, Ofori-Asenso, R, Mazidi, M, Mazloomi, SM
Phytotherapy research : PTR. 2020;(7):1587-1598
Abstract
The therapeutic potential of green tea as a rich source of antioxidants and anti-inflammatory compounds has been investigated by several studies. The present study aimed to systematically review and analyze randomized clinical trials (RCTs) assessing the effects of green tea, catechin, and other forms of green tea supplementation on levels of liver enzymes. PubMed, SCOPUS, EMBASE, and Cochrane databases were searched until February 2019. All RCTs investigating the effect of green tea or its catechin on liver enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin were included. A total of 15 RCTs were included. The overall effect of green tea on liver enzymes was nonsignificant (ALT [Standardized mean difference (SMD)= -0.17, CI -0.42 to 0.08, p = .19], AST [SMD = -0.07, CI -0.43 to 0.29, p = .69], and ALP [SMD = -0.17, CI -0.45 to 0.1, p = .22]). However, subgroup analyses showed that green tea reduced the levels of liver enzymes in participants with nonalcoholic fatty liver disease (NAFLD) but in healthy subjects, a small significant increase in liver enzymes was observed. In conclusion, the results of this study suggest that the effect of green tea on liver enzymes is dependent on the health status of individuals. While a moderate reducing effect was observed in patients with NAFLD, in healthy subjects, a small increasing effect was found.