Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients. METHOD: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an intervention (I) or control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, while C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT. DISCUSSION: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on the efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration - ClinicalTrials.gov : NCT03749070. November 21, 2018.

Nonalcoholic fatty liver disease in adolescents with phenylketonuria.

OBJECTIVE: This study aimed to investigate non-alcoholic fatty liver disease (NAFLD) occurrence and factors associated with the disease in phenylketonuria (PKU) patients undergoing exclusive dietary treatment. METHOD: This cross-sectional study included 101 adolescents 10 to < 20 years of age with PKU, who were undergoing exclusive dietary treatment and monitored since early diagnosis at a single reference service. Anthropometric and biochemical assessments were performed and food intake was documented, and an ultrasound diagnosis of NAFLD was established. Data were evaluated using the Student's t-test for continuous variables, the chi-square for categorical variables, and logistic regression using the Wald chi-squared test; differences with p < 0.05 were considered to be statistically significant. RESULTS: NAFLD was detected in 26 (25.7%) teenagers. There was no difference in prevalence between the sexes or nutritional status. The final logistic regression model revealed low sensitivity (26.1%) and high specificity (94.7%). The specificity suggested a lower likelihood of NAFLD in older adolescents, in the presence of normal or high levels of alkaline phosphatase, lower carbohydrate intake, and adequate protein and lipid intake. CONCLUSIONS: The prevalence of NAFLD in adolescents with PKU was higher than that found in healthy Brazilian adolescents and similar to that found in obese Brazilian children, suggesting a higher risk for NAFLD in patients with PKU treated exclusively by dietary modification.

Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2.

Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients.

Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis.

AIM: To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases. METHODS: A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention. RESULTS: An amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis. CONCLUSION: Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.

Malnutrition and Nutritional Support in Alcoholic Liver Disease: a Review.

Malnutrition is associated with alcoholic liver disease (ALD) and related complications such as hepatic encephalopathy and increased rate of infections. Avoidance of prolonged fasting and overly restrictive diets is important to avoid poor nutrition. Adequate intake of calories, protein, and micronutrients via frequent small meals and evening supplements and/or enteral and parenteral nutrition when indicated has been associated with reduced mortality and morbidity in patients with ALD. Modification of protein/fat sources and composition in addition to probiotic supplementation are promising interventions for decreased progression of ALD and its complications.

Factors Associated with Insulin Resistance in Patients with Chronic HCV Genotype 1 Infection without Obesity or Type 2 Diabetes.

OBJECTIVE: To investigate the prevalence of insulin resistance (IR) and its association with clinical parameters in patients with hepatitis C virus (HCV) genotype 1 without obesity or type 2 diabetes. METHODS: One hundred and twenty-seven HCV-infected patients admitted to the Nutrition and Hepatology Clinic were included. Statistical analysis was performed using the Mann-Whitney test, Fisher's exact test, and Poisson regression analysis. RESULTS: The prevalence of IR (homeostasis model assessment [HOMA]-IR ≥ 3.0) was 37.0%. The independent predictors for IR included the following: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper normal limit (odds ratio [PR] = 2.06, 95% CI, 1.16-3.66; PR = 2.32, 95% CI, 1.26-4.49, respectively); gamma glutamyl transferase (γGT) ≥ 85 U/L (PR = 2.09, 95% CI, 1.12-4.12); increased waist circumference (PR = 2.24, 95% CI, 1.25-4.17); increased waist : hip ratio (PR = 2.24, 95% CI, 1.11-5.17); increased body fat percentage (PR = 2.21, 95% CI, 1.01-5.79); overweight (PR = 2.54, 95% CI, 1.40-4.82); and metabolic syndrome (PR = 3.05, 95% CI, 1.69-5.44). High ALT levels and anthropometric parameters remained in the model of multivariate regression analysis. CONCLUSIONS: Our findings showed a significantly high prevalence of insulin resistance in nondiabetic, nonobese patients with hepatitis C genotype 1. High ALT levels and anthropometric parameters were significantly associated with IR after multivariate regression analysis. Our data show the importance of monitoring IR, weight, and body composition in patients with chronic hepatitis C. Nutritional management seems to be important in the control of comorbidities related to excess weight and the enhancement of therapeutic responses.

Tolerance to enteral nutrition therapy in traumatic brain injury patients.

OBJECTIVE: To evaluate the tolerance to enteral nutrition (EN) and the effects of pro-kinetic drugs in critical traumatic brain injury (TBI) patients. METHODS: Transversal observational study. A total of 32 out of 45 TBI patients of both genders receiving EN were evaluated in a trauma referral hospital intensive care unit (ICU). Data from each patient were collected for a period of 10 consecutive days after initiation of enteral feeding: gastric residue, presence of vomiting, abdominal distension, Glasgow coma scale and the use of pro-kinetic agents. RESULTS: In 20 of the 32 patients high levels of gastric residue were found. Of these 20 patients, half could not tolerate the diet within the first 72 hours following infusion. However, no association was found between disease severity and occurrence of gastrointestinal complications (p > 0.05). Feeding intolerance was observed in 75.0% (n = 24) of patients, even with the systematic use of metaclopramide from the outset of nutritional therapy. All patients with feeding intolerance who used erythromycin by nasogastric tube showed improvement. CONCLUSIONS: The high level of gastric residue was the most common feeding intolerance and the delivery of erythromycin by nasogastric tube seems to control gastrointestinal disorders in TBI patients.