The increased amount of coffee consumption lowers the incidence of fatty liver disease in Korean men.

BACKGROUND AND AIMS: Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults. METHODS AND RESULTS: Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in "increase" group comparing with "no change" group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females. CONCLUSIONS: The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver.

Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study.

BACKGROUND/AIMS: The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant. METHODS: Twenty subjects with hepatic steatosis (50% women, age 18-77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared. RESULTS: Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0-431.0] vs. 564.5 [range 509.0-682.0] µmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group. CONCLUSIONS: Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.

Four Weeks of Preoperative Omega-3 Fatty Acids Reduce Liver Volume: a Randomised Controlled Trial.

PURPOSE: Weight loss before bariatric surgery with a low-calorie diet (LCD) has several advantages, including reduction of liver volume and an improved access to the lesser sac. Disadvantages include performing surgery in a state of undernutrition, side effects, costs and patient compliance. Omega-3 fatty acids may serve as an alternative to reduce liver steatosis. MATERIALS AND METHODS: A randomised controlled open-label trial was done to compare the effects of a LCD with Modifast (800 kcal/day) during 2 weeks with 2 g of omega-3 fatty acids a day and a normal diet (2000 kcal/day) during 4 weeks. Total liver volume (TLV) and volume of the left liver lobe (LLL), visceral fat area (VFA) and muscle area (SMA) at the L3-L4 level were measured with MRI before and after preoperative treatment. RESULTS: Sixty-two morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) were recruited. In both groups, there was a significant decrease in LLL, TLV and VFA. For LLL and TLV reduction, the LCD had a significantly larger effect (p < 0.05). Only in the LCD group was there a significant decrease in SMA with significantly more side effects and worse compliance. CONCLUSION: Both the LCD and omega-3 diet reduced LLL, TLV and VFA. The LCD outperformed the omega-3 diet in LLL and TLV reduction, but induced significant loss of SMA and had worse compliance due to more side effects. Omega-3 fatty acids may provide a safe and more patient-friendly alternative for a LCD and further research is indicated. TRIAL REGISTRATION: The study is registered at www.clinicaltrials.gov (NCT02206256).

Ether-phosphatidylcholine characterized by consolidated plasma and liver lipidomics is a predictive biomarker for valproic acid-induced hepatic steatosis.

Valproic acid (VPA) is known to induce hepatic steatosis due to mitochondrial toxicity in rodents and humans. In the present study, we administered VPA to SD rats for 3 or 14 days at 250 and 500 mg/kg and then performed lipidomics analysis to reveal VPA-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. VPA induced hepatic steatosis at the high dose level without any degenerative changes in the liver on day 4 (after 3 days dosing) and at the low dose level on day 15 (after 14 days dosing). We compared the plasma and hepatic lipid profiles obtained on day 4 between the VPA-treated and control rats using a multivariate analysis to determine differences between the two groups. In total, 36 species of plasma lipids and 24 species of hepatic lipids were identified as altered in the VPA-treated group. Of these lipid species, ether-phosphatidylcholines (ePCs), including PC(16:0e/22:4) and PC(16:0e/22:6), were decreased in both the plasma and liver from the low dose level on day 4, however, neither an increase in hepatic TG level nor histopathological hepatic steatosis was observed at either dose level on day 4. Hepatic mRNA levels of glycerone-phosphate O-acyltransferase (Gnpat), which is a key enzyme for biosynthesis of ePC, was also decreased by treatment with VPA along with the decrease in ePCs. In conclusion, the changes in ePCs, (PC[16:0e/22:4] and PC[16:0e/22:6]), have potential utility as predictive biomarkers for VPA-induced hepatic steatosis.

Coffee Intake and Liver Steatosis: A Population Study in a Mediterranean Area.

Coffee drinking seems to have several beneficial effects on health outcomes. However, the effect on hepatic steatosis, depending on a high alcohol consumption (AFLD, alcoholic fatty liver disease) or on metabolic factors (non-alcoholic fatty liver disease, NAFLD), is still equivocal. Thus, we aimed to explore the potential association between coffee consumption and the presence and severity of hepatic steatosis in people with NAFLD or AFLD. In this cross-sectional study, coffee drinking was recorded using a semi-quantitative food frequency questionnaire, and categorized as yes vs. no and as 0, 1, 2, ≥3. The degree of fatty liver was assessed through a standardized ultrasound examination (score 0 to 6, with higher values reflecting higher severity). Liver steatosis was classified as NAFLD or AFLD on daily alcohol intake >30 g/day for men and >20 g/day for women. This study included 2819 middle-aged participants; the great majority were coffee drinkers (86.1%). After adjusting for 12 potential confounders, drinking coffee was not associated with decreased odds for NAFLD (n = 916) (odds ratio, OR = 0.93; 95% confidence intervals, CI: 0.72-1.20) or AFLD (n = 276) (OR = 1.20; 95% CI: 0.66-2.0). The consumption of coffee (categorized as yes vs. no), or an increased consumption of coffee were not associated with the presence of mild, moderate or severe liver steatosis in either NAFLD or AFLD. In conclusion, coffee intake was not associated with any lower odds of hepatic steatosis in either non-alcoholic or alcoholic forms in this large cohort of South Italian individuals.

Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic ß cell proliferation after the withdrawal of OSI-906.

Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and ß cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.

High-fat diet-induced plasma protein and liver changes in obese rats can be attenuated by melatonin supplementation.

Obesity triggers changes in protein expression in various organs that might participate in the pathogenesis of obesity. Melatonin has been reported to prevent or attenuate such pathological protein changes in several chronic diseases. However, such melatonin effects on plasma proteins have not yet been studied in an obesity model. Using a proteomic approach, we investigated the effect of melatonin on plasma protein profiles after rats were fed a high-fat diet (HFD) to induce obesity. We hypothesized that melatonin would attenuate abnormal protein expression in obese rats. After 10weeks of the HFD, animals displayed increased body weight and fat accumulation as well as increased glucose levels, indicating an obesity-induced prediabetes mellitus-like state. Two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry revealed 12 proteins whose expression was altered in response to the HFD and the melatonin treatment. The altered proteins are related to the development of liver pathology, such as cirrhosis (α1-antiproteinase), thrombosis (fibrinogen, plasminogen), and inflammation (mannose-binding protein A, complement C4, complement factor B), contributing to liver steatosis or hepatic cell death. Melatonin treatment most probably reduced the severity of the HFD-induced obesity by reducing the amplitude of HFD-induced plasma protein changes. In conclusion, we identified several potential biomarkers associated with the progression of obesity and its complications, such as liver damage. Furthermore, our findings reveal melatonin's beneficial effect of attenuating plasma protein changes and liver pathogenesis in obese rats.

Diagnóstico de esteatosis hepática por métodos clínicos, bioquímicos y por imágenes / Diagnosis of hepatic steatosis using clinical, biochemical and imaging methods

La enfermedad hepática grasa no alcohólica comprende un espectro de afecciones hepáticas que va desde la simple esteatosis a la esteatohepatitis, fibrosis y hasta cirrosis. Su prevalencia aumenta con la edad, la obesidad y está fuertemente asociada con la presencia de síndrome metabólico y aumento de la mortalidad cardiovascular y por enfermedades malignas. Se produce por una acumulación de triglicéridos en los hepatocitos relacionada con insulinorresistencia hepática y muscular. Su presencia se asocia con aumento de transaminasa glutámico-oxaloacética o glutamico-pirúvica, aunque esta última puede no estar elevada en la enfermedad avanzada. Existen 5 índices utilizados para el diagnóstico de esteatosis hepática: SteatoTest, fatty liver index, NAFLD liver fat score, lipid acumulation product y hepatic steatosis index, mientras que para esteatohepatitis contamos con el NASH test, NASH diagnostics, NASH score y HAIR (Hypertention, increased ALT and IR o Insulin resistence). En estadios de fibrosis el índice transaminasa glutamicooxáloacetica-glutamicopiruvica aumenta, así como la ferritina en sangre y el valor del NAFLD fibrosis score, siendo de alta especificidad para el diagnóstico. La ecografía abdominal tiene una gran disponibilidad, pero su sensibilidad diagnóstica es menor cuando existen grados leves de infiltración grasa hepática. La tomografía computada tiene una especificidad del 100% cuando el contenido graso es mayor al 30% pero la radiación emitida no permite un uso frecuente. La resonancia magnética con espectroscopia constituye el método de elección para la detección y cuantificación de contenido de grasa hepática. La biopsia hepática es un método invasivo que permite una clasificación pronóstica adecuada de la enfermedad, pero por sus complicaciones solo debe realizarse en pacientes seleccionados: aquellos con riesgo elevado de esteatohepatitis o riesgo de fibrosis por laboratorio o clínica, o con otras enfermedades hepáticas coexistentes. La identificación temprana de enfermedad hepática grasa no alcohólica permite la implementación de medidas tempranas para disminuir la morbimortalidad asociada a esta condición.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver diseases ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. Its prevalence increases with age and with obesity, and is strongly associated with the presence of metabolic syndrome and increased cardiovascular and malignant diseases. It is caused by an accumulation of triglycerides in liver hepatocytes and muscles, and related to insulin resistance. Its presence is associated with the increase of alanine aminotransferase (alt), although it may not be elevated in advanced disease. There are 5 indexes used for the diagnosis of hepatic steatosis: SteatoTest, fatty liver index, NAFLD liver fat score, lipid accumulation product and hepatic steatosis index, whereas for esteatohepatitis the NASH test, NASH diagnostics, as well as the non-alcoholic steatohepatitis (NASH) score and HAIR (hypertension, ALT, and insulin resistance). In stages of fibrosis AST-ALT index increases as well as ferritin in blood and the NAFLD fibrosis score, which has a high specificity for diagnosis. Abdominal ultrasound is widely available, but its diagnostic sensitivity is lower when there are mild degrees of hepatic fatty infiltration. Computed tomography has a specificity of 100% when fat content is greater than 30%, but the radiation emitted prevents frequent use. Magnetic resonance spectroscopy is the method of choice for the detection and quantification of liver fat content. Liver biopsy is an invasive method that enables appropriate prognostic classification of the disease, but has some complications, and should only be performed in selected individuals: high risk of steatohepatitis or fibrosis risk of laboratory or clinical or other co-existing liver disease. Early identification of NAFLD allows early measures to be implemented in order to reduce morbidity and mortality associated with this condition.

Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens.

Background: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model.Objective: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis.Methods: Hy-Line W-36 laying hens were fed standard feed from 25 to 45 wk of age to induce fatty liver. They were killed every 4 wk, and liver and plasma were collected at each time point to assess fatty liver development and for transcriptomic and proteomic analysis. Next, selected biomarkers were confirmed in additional experiments by providing supplements of the hepatoprotective nutrients betaine [300, 600, or 900 parts per million (ppm) in vivo; 2 mM in vitro] or docosahexaenoic acid (DHA; 1% in vivo; 100 µM in vitro) to 30-wk-old Hy-Line W-36 laying hens for 4 mo and to Hy-Line W-36 chicken primary hepatocytes with oleic acid-induced steatosis. Liver or hepatocyte lipid contents and the expression of biomarkers were then examined.Results: Plasma acetoacetyl-CoA synthetase (AACS), dipeptidyl-peptidase 4 (DPP4), glutamine synthetase (GLUL), and glutathione S-transferase (GST) concentrations are well-established biomarkers for NAFLD. Selected biomarkers had significant positive associations with hepatic lipid deposition (P < 0.001). Betaine (900 ppm in vivo; 2 mM in vitro) and DHA (1% in vivo; 100 µM in vitro) supplementation both resulted in lower steatosis accompanied by the reduced expression of selected biomarkers in vivo and in vitro (P < 0.05).Conclusion: This study used adult laying hens to identify biomarkers for NAFLD and indicated that AACS, DPP4, GLUL, and GST could be considered to be potential diagnostic indicators for NAFLD in the future.

Noninvasive Swansea criteria are valuable alternatives for diagnosing acute fatty liver of pregnancy in a Chinese population.

BACKGROUND: This study aims to assess the diagnostic and prognostic value of Swansea criteria in diagnosing acute fatty liver of pregnancy (AFLP) in a Chinese population. METHODS: A retrospective study was conducted on 52 Chinese women diagnosed with AFLP. All selected cases were reassessed using the Swansea criteria with special focus on the noninvasive criteria, since performing a liver biopsy for this indication is rare in a Chinese population. RESULTS: Ninety point four percent of patients fulfilled five or more of the Swansea criteria. Thirty-one cases were positive for six or more Swansea criteria, but there were no significance differences between patients when using a cutoff criteria <6 or >6. When patients were positive for less than seven criteria, frequency of stillbirth, continuous blood purification (CBP) treatment, hysterectomy, and postpartum hemorrhage were not increased. However, patients who were positive for seven or more criteria had a significantly higher risk of stillbirth and a higher rate of CBP treatment (p < 0.05). Areas under the receiver operating characteristic (ROC) curve of postpartum hemorrhage was 0.670, which reached a statistical significance (p = 0.040). We observed a significantly elevated postpartum hemorrhage along with positivity of the Swansea criteria (p = 0.040). CONCLUSIONS: Swansea criteria without liver biopsy are good screening tools for AFLP diagnosis, and may be useful for assessing disease severity.

Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects.

AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants. METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme. RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P < 0.05] and γ-GTP [before: 51.5 (40.8-91.3) vs after: 50.0 (37.8-85.3) IU/L, P < 0.05], as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66 (5.51-9.03) vs after: 5.49 (4.89-6.66) ng/mg-creatinine, P < 0.05]. The reduction of urinary 8-OHdG was significantly correlated with decreased levels of both ALT and γ-GTP [∆8-OHdG and ∆ALT: Spearman r (r) 0.514 and P = 0.012, ∆8-OHdG and ∆γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01). CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.

Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial ß-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis induced by capecitabine and oxaliplatin in a 36-year-old woman.

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

[Non-alcoholic fatty liver disease and steatohepatitis]. / Nem alkoholos zsírmáj és zsírmájhepatitis.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

Hair selenium levels in hepatic steatosis patients.

The purpose of this study was to assess hair selenium levels of liver patients suffering from hepatic simple steatosis and non-alcoholic steatohepatitis (NASH) in central areas of China. Selenium was measured by an atomic absorption spectrophotometer equipped with the hydride generation system. The levels of selenium in healthy individuals ranged between 0.3 and 0.9 µg/g, and mean hair selenium levels in the male population and female population were 0.59 ± 0.18 and 0.57 ± 0.15 µg/g, respectively. These concentrations did not vary significantly (P > 0.05) in relation to the gender. One hundred-eighteen individuals of both sexes aged between 15 and 60 years with hepatic simple steatosis and NASH were selected for this study. The mean and standard deviation of hair selenium concentrations observed in male and female patients with hepatic simple steatosis were 0.54 ± 0.16 and 0.50 ± 0.15 µg/g, respectively, while the mean and standard deviation of hair selenium concentrations observed in male and female patients with NASH were 0.40 ± 0.14 and 0.41 ± 0.12 µg/g. Analysis of t test showed a significant difference between NASH (P < 0.001) patients in hair selenium concentrations when compared with controls.

Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S. METHODS AND RESULTS: Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37-75 nmol/L [15-30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064-0.96, P=0.02). CONCLUSION: Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Investigation of the effects of Chlorella vulgaris supplementation in patients with non-alcoholic fatty liver disease: a randomized clinical trial.

BACKGROUND/AIMS: To investigate the advantage of Chlorella vulgaris supplementation as an adjunctive therapy in patients with non-alcoholic fatty liver disease (NAFLD). METHODOLOGY: In a randomized, open-label clinical trial, 76 individuals with NAFLD were randomly assigned to: 1) Chlorella group (n=33), receiving C. vulgaris extract (1200 mg/day) + metformin (750 mg/ day) + vitamin E (200 mg/day) for 3 months, or 2) Metformin group (n=43), receiving metformin (1250 mg/ day) + vitamin E (200 mg/day) for 3 months. Weight, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), insulin, total and direct bilirubin, fasting blood sugar (FBS), glycated hemoglobin (HbA1c), uric acid, albumin and lipid profile were evaluated at baseline and at the end of trial. RESULTS: Weight and BMI were decreased in both groups. Serum ALT, AST, triglycerides, uric acid, HbA1c and HOMA-IR index were reduced only in the Chlorella group whereas significant changes in total cholesterol, LDL, HDL and FBS were only observed in the metformin group. There were also borderline significant reductions in insulin and FBS in the Chlorella group. CONCLUSIONS: The findings of the present trial indicated that addition of C. vulgaris extract to the therapeutic regimen of NAFLD including metformin and vitamin E, is associated with favorable effects on serum levels of transaminases, triglycerides as well as insulin sensitivity. Therefore, C. vulgaris extract might be a promising hepatoprotective supplement for patients with NAFLD.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive oil) which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.