Steatosis In Non-alcoholic Fatty Liver Disease Patients Research Articles

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).

Ultrasound Attenuation Imaging vs MRI-PDFF, Echogenicity and Liver Function for Assessing Degree of Steatosis in NAFLD and Non-NAFLD Patients.

Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.

Diagnostic value of FibroTouch in identifying hepatic steatosis in NAFLD with MRI-PDFF as the reference standard.

To estimate the performance of the FibroTouch-based ultrasound attenuation parameter (UAP) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD), with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. This prospective, cross-sectional study included 275 individuals in the training group and 110 individuals in the validation group, all of whom completed a standardized research visit, laboratory tests, MRI-PDFF, and UAP measurements over 1 month. Pearson correlation coefficient and Bland-Altman analysis were used to assess the agreement between UAP and MRI-PDFF for the detection of hepatic steatosis. The diagnostic value of UAP was evaluated by the area under the receiver operating characteristic (ROC) curve (AUROC). Confounding factors to UAP performance were identified by ROC curves and regression analyses. The AUROC of UAP for detecting MRI-PDFF at ≥5%, ≥10%, and ≥20% were 0.95 (95% confidence interval [CI] 0.92-0.97), 0.86 (95% CI 0.81-0.90), and 0.90 (95% CI 0.86-0.93), respectively, and their optimal thresholds were 259, 274, and 295 dB/m, respectively. The UAP measurements had higher diagnostic accuracy in participants with lower waist circumference (≤90 cm for men and ≤80 cm for women) compared to those with higher waist circumference (AUROC values: 0.97 vs 0.84, P < 0.05). Bland-Altman analysis showed good agreement between UAP and MRI-PDFF (bias 0.00021). According to established regression analyses, hepatic steatosis could be accurately diagnosed using UAP estimation. FibroTouch-UAP has a high diagnostic potential for hepatic steatosis in NAFLD patients and helps clinical assessment and monitoring.

Quantitative Diagnosis of Nonalcoholic Fatty Liver Disease with Ultrasound Attenuation Imaging in a Biopsy-Proven Cohort

To evaluate the performance of attenuation imaging (ATI) based on ultrasound for detection of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). This prospective study was approved by our institutional review board (B2021-092R). Written informed consent was obtained from all patients. This study included 60 patients who had clinical suspicion of NAFLD and were referred for liver biopsy after ATI and controlled attenuation parameter (CAP) examinations between September 2020 and December 2021. The histologic hepatic steatosis was graded. The area under curve (AUC) analysis was performed. The success rate of the ATI examination was 100%. The intraobserver reproducibility of ATI was 0.981. The AUCs of ATI for detecting ≥S1, ≥S2, and S3 were 0.968 (cut-off value of 0.671dB/cm/MHz), 0.911 (cut-off value of 0.726dB/cm/MHz), and 0.766 (cut-off value of 0.757dB/cm/MHz), respectively. The AUCs of CAP for detecting ≥S1, ≥S2, and S3 were 0.916 (cut-off value of 258.5dB/m), 0.872 (cut-off value of 300.0dB/m), and 0.807 (cut-off value of 315.0dB/m), respectively. The diagnostic values showed no significant difference between ATI and CAP in detecting ≥S1, ≥S2, and S3 (P=.281, P=.254, and P=.330, respectively). The ATI had significant correlations with high-density lipoprotein cholesterol (P<.001), and with triglycerides (P=.015). ATI showed good feasibility and diagnostic performance in the detection of varying degrees of hepatic steatosis in NAFLD patients.

Non-invasive assessment of hepatic fibrosis and steatosis by FibroScan in Egyptian children and adolescents with nonalcoholic fatty liver disease: A single center study

Background Pediatric nonalcoholic fatty liver disease (NAFLD) has been recognized as a global health problem in pediatric. Owing to the limitations of the liver biopsy and the importance of screening and follow-up of NAFLD patients for hepatic steatosis and fibrosis, the noninvasive diagnostic methods are obviously needed. Abdominal ultrasonography has several limitations to assess the degree of fatty liver. Recently; transient elastography (TE, FibroScan) with controlled attenuation parameter (CAP) has been emerging as a relevant tool for assessing hepatic fibrosis and steatosis. The aim of this study was the noninvasive evaluation of hepatic fibrosis and steatosis by FibroScan with CAP through measuring liver stiffness and CAP values, respectively, in Egyptian children and adolescents with NAFLD proven by ultrasound. Patients and methods 60 children and adolescents proven as NAFLD patients with ultrasound, were subjected to clinical examination and anthropometric measurements, liver enzymes (serum ALT, AST, ALP), lipid profile, fasting blood glucose (FBG) level and fasting serum insulin. Insulin resistance was calculated by homeostasis model assessment method of insulin resistance HOMA-IR. Hepatic fibrosis and steatosis were assessed by measuring liver stiffness and CAP, respectively, using FibroScan. Results There were significant increasing of the laboratory data among NAFLD patients with increasing the ultrasonographic grades of liver steatosis (P=0.0001, liver steatosis score (CAP stage) by fibroscan (P=0.0001) and liver fibrosis degree by fibroscan among patients (P=0.0001). CAP values by FibroScan are significantly increasing parallel to the grades of ultrasonic steatosis in NAFLD patients with different grades of ultrasonic steatosis. Also, the values of liver stiffness by FibroScan are significantly increasing parallel to the grades of ultrasonic steatosis in NAFLD patients with different grades of ultrasonic steatosis. There were positive correlations between ultrasonic steatosis grades and each of CAP value, liver stiffness value among the studied NAFLD children. Conclusion The data confirmed that Transient Elastography (TE) with CAP is a useful tool for detection of hepatic steatosis and fibrosis. There were positive correlations between ultrasonic steatosis grades and each of CAP value, liver stiffness value among the NAFLD children.

The Accuracy and Clinical Relevance of the Multi-echo Dixon Technique for Evaluating Changes to Hepatic Steatosis in Patients with Non-alcoholic Fatty Liver Disease Treated with Formulated Food.

The Multi-echo Dixon (ME-Dixon) is a non-invasive quantitative MRI technique to diagnose non-alcoholic fatty liver disease (NAFLD). In this study, the hydrogen proton MR spectroscopy (1H-MRS) was used as a reference to explore the accuracy of the ME-Dixon technique in evaluating hepatic steatosis in NAFLD patients after ingesting formulated food and its correlation with changes in clinical indicators. Twenty-seven patients with NAFLD were enrolled. Fifteen patients completed 12 weeks of treatment with prebiotics and dietary fiber. In addition, abdominal MRI scans and blood tests were performed before and after treatment. The MRI-proton density fat fraction (MRI-PDFF) and MRS-PDFF were measured using the ME-Dixon and 1H-MRS techniques. The Bland-Altman method and Pearson correlation analysis were used to test the consistency of the two techniques for measuring the liver fat content and the changed values. Besides, correlation analysis was conducted between the MRI-PDFF value and metabolic indicators. In the PDFF quantification of 42 person-times and the monitoring of the PDFF change in 15 patients under treatment, there was a good consistency and a correlation between MRI and MRS. At baseline, MRI-PDFF was positively correlated with insulin resistance index (HOMA-IR), fatty liver index (FLI), and liver enzymes. After treatment, the changes in MRI-PDFF were positively correlated with the recovery degree of FLI and liver enzymes. ME-Dixon has a good consistency and a correlation with MRS in quantifying the liver fat content and monitoring the treatment effect, which may be used as an accurate indicator for clinical monitoring of changes in the liver fat content.

Azonal steatosis correlates with disease severity and poor outcome of nonalcoholic fatty liver disease

In this study we aimed to assess the clinicopathological characteristics and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. Clinicopathological data of 238 individuals with biopsy-confirmed NAFLD were collected. Nonalcoholic steatohepatitis-clinical research network (NASH-CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver-related events (LREs) was compared by Kaplan-Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan-acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34-27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6-year follow-up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06-1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98-11.47, P = 0.053) might also play a role. AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role.

The role of PNPLA3 (rs738409) c>g variant on histological progression of non-alcoholic fatty liver disease.

Background and AimThe present study aims to investigate the role of genetic variability of the PNPLA3 gene (adiponectin) in predisposition to non-alcoholic fatty liver disease (NAFLD) by comparing NAFLD patients to healthy controls and to investigate any impact of the PNPLA3 genetic variability on the natural course of the disease.Materials and MethodsThis cohort consisted of 174 patients with biopsy-proven NAFLD and 151 healthy controls. DNA was extracted from peripheral blood and the rs738409 C>G single nucleotide polymorphism was assessed using PCR-DNA sequencing.ResultsThe frequency distribution of the GG genotype was significantly higher in NAFLD patients than in controls (p=0.01). In patients with NAFLD, the GG genotype was associated with lower platelet counts (p=0.001), the presence of steatohepatitis (p=0.04) and hepatic fibrosis (p=0.016). After adjustment for age, gender, obesity, and diabetes mellitus, the GG genotype was an independent predictor of significant hepatic fibrosis (adjusted odds ratio =3.031 p=0.012). From the baseline to sequential liver biopsies, the progression of NAS in NAFLD patients was slightly higher in the GG genotype than that of CC and GG genotypes (p=0.18).ConclusionThe PNPLA3 GG genotype is a predisposing factor for the development of hepatic steatosis in NAFLD patients and related to a more severe liver disease.

Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p < 0.001), insulin levels (p < 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), and CAP value (p < 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p < 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients.

Ramadan fasting improves liver function and total cholesterol in patients with nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious global health problem, thus the prevention and management of the disease is necessary. This study aimed to determine the effects of Ramadan Fasting (RF) on liver function, Visceral Adiposity Index (VAI) and Atherogenic Index of Plasma (AIP) in these patients. Eighty-three NAFLD patients (57 males and 26 females) were enrolled in the study, 42 patients who practiced RF, between Jun 18 through July 17, 2015 and 41 patients in non-fasting groups. Anthropometric parameters and Ultrasound grading were measured before and after Ramadan. The biochemical parameters including lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), liver enzymes (Aspartate aminotransferase, SGOT and Alanine aminotransferase, SGPT) were evaluated before and after Ramadan. AIP and VAI were calculated based on formula. The mean decreases in anthropometric indices were significantly different between groups. Similarly, the mean decrease in the total cholesterol values in the fasting group was remarkably greater than in the control group (p=0.02). The values of AIP and VAI decreased at the end of the study in both group and the mean of changes showed no differences between groups (p=0.79 and p=0.65 for AIP and VAI, respectively). The changes in the concentrations of liver enzymes, as well as the severity of hepatic steatosis, showed remarkable differences between groups (p=0.03, p=0.05, and p=0.02 for SGOT and SGPT, and Liver steatosis, respectively). RF improved liver steatosis in NAFLD patients and might be useful in the management of NAFLD.

The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review.

Non-alcoholic fatty liver disease (NAFLD) is currently considered an important component of metabolic syndrome (MetS). The spectrum of NAFLD includes conditions that range from simple hepatic steatosis to non-alcoholic steatohepatitis. NAFLD is correlated with liver-related death and is predicted to be the most frequent indication for liver transplantation by 2030. Insulin resistance is directly correlated to the central mechanisms of hepatic steatosis in NAFLD patients, which is strongly correlated to the imbalance of the renin–angiotensin system, that is involved in lipid and glucose metabolism. Among the emerging treatment approaches for NAFLD is the anti-hypertensive agent telmisartan, which has positive effects on liver, lipid, and glucose metabolism, especially through its action on the renin–angiotensin system, by blocking the ACE/AngII/AT1 axis and increasing ACE2/Ang(1–7)/Mas axis activation. However, treatment with this drug is only recommended for patients with an established indication for anti-hypertensive therapy. Thus, there is an increased need for large randomized controlled trials with the aim of elucidating the effects of telmisartan on liver disease, especially NAFLD. From this perspective, the present review aims to provide a brief examination of the pathogenesis of NAFLD/NASH and the role of telmisartan on preventing liver disorders and thus to improve the discussion on potential therapies.

Controlled attenuation parameter using the FibroScan® XL probe for quantification of hepatic steatosis for non-alcoholic fatty liver disease in an Asian population.

The FibroScan® XL probe reduces failure of liver stiffness measurement (LSM) and unreliable results in obese patients. The objective of this article is to evaluate the accuracy of controlled attenuation parameter (CAP) obtained using the XL probe for the estimation of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). Adult NAFLD patients with a liver biopsy within six months were included and were examined with the FibroScan® M and XL probes. Histopathological findings were reported according to the Non-Alcoholic Steatohepatitis Clinical Research Network Scoring System. Participants who did not have fatty liver on ultrasonography were recruited as controls. A total of 57 NAFLD patients and 22 controls were included. The mean age of the NAFLD patients and controls was 50.1 ± 10.4 years and 20.2 ± 1.3 years, respectively (p = 0.000). The mean body mass index was 30.2 ± 5.0 kg per m2 and 20.5 ± 2.4 kg per m2, respectively (p = 0.000). The distribution of steatosis grades were: S0, 29%; S1, 17%; S2, 35%; S3, 19%. The AUROC for estimation of steatosis grade ≥ S1, S2 and S3 was 0.94, 0.80 and 0.69, respectively, using the M probe, and 0.97, 0.81 and 0.67, respectively, using the XL probe. CAP obtained using the XL probe had similar accuracy as the M probe for the estimation of hepatic steatosis in NAFLD patients.

The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial.

Background:Regarding to the growing prevalence of nonalcoholic fatty liver disease (NAFLD), concentrating on various strategies to its prevention and management seems necessary. The aim of this study was to determine the effects of symbiotic on C-reactive protein (CRP), liver enzymes, and ultrasound findings in patients with NAFLD.Methods:Eighty NAFLD patients were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Participants received symbiotic in form of a 500 mg capsule (containing seven species of probiotic bacteria and fructooligosaccharides) or a placebo capsule daily for 8 weeks. Ultrasound grading, CRP, and liver enzymes were evaluated at the baseline and the end of the study.Results:In the symbiotic group, ultrasound grade decreased significantly compared to baseline (P < 0.005) but symbiotic supplementation was not associated with changes in alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. In the placebo group, there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased (P = 0.002, P = 0.02, respectively). CRP values remained static in either group.Conclusions:Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression.

English

INTRODUCTION: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. This study aims to elucidate serum levels of Vitamin B12 in south Indian NAFLD patients. AIM: To investigate the correlation between Vitamin B 12 and NAFLD. MATERIALS AND METHODS: The study was designed as a case control study. Patients diagnosed to have NAFLD by standard clinical, radiological and biochemical investigations formed the study group. Healthy volunteers formed the control group. Fasting blood samples were collected at Star medical diagnostics and were subjected to biochemical analysis. Vitamin B12 was assayed using chemiluminiscence commercial kits. RESULTS: A total of 158 subjects were enrolled in the study. Cases constituted 79 and an equal number of controls were chosen by matching. Vitamin B 12 deficiency (<223 picograms/ml), was observed in 43% of NAFLD patients and none in the control group. CONCLUSION: Our results indicate that Vitamin B 12 deficiency may be one of the factors responsible for hepatic steatosis in NAFLD patients.

Relationship between serum vitamin b12, hyperhomocysteinemia in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) represents a wide spectrum of liver damage and the prevalence is increasing worldwide. Hyper homocysteinemia is implicated as a causative factor of endothelial dysfunction, hepatic steatosis and cardio vascular disease (CVD). Since Vitamin B12 deficiency is one of the most important causative factors of hyper homocysteinemia. This study aims to elucidate serum levels of homocysteine and Vitamin B12 in south indian NAFLD patients. Patient diagnosed to have NAFLD by standard clinical, radiological and biochemical investigations formed the study group. Healthy volunteers formed the control group. Fasting blood samples were collected at Star medical diagnostics and were subjected to biochemical analysis. Vitamin B12 and homocysteine were assayed using chemiluminiscence commercial kits. Liver function tests (LFT), lipid profile and HOMA IR were assayed using auto analyzer. Vitamin B 12 deficiency ( 17.24 micro moles). Elevated ALT was found to be correlated with 67% of Vitamin B12 and 70% of hyper homocysteinemic NAFLD patients respectively. Our results indicate that hyper homocysteinemia may be one of the factors responsible for hepatic steatosis in NAFLD patients.

Visceral adipose tissue visfatin in nonalcoholic fatty liver disease

Background. Visfatin is a novel adipocytokine predominantly expressed and secreted by visceral adipose tissue. It is realized for its multiple functions of central importance in NAD biosynthesis, innate immunity and inflammation. Its phosphoribosyl transferase activity regulates cellular energetics and NAD dependent enzymes such as SIRTUINS. Although its expression in various tissues and circulating levels are documented, visceral visfatin levels in Nonalcoholic fatty liver disease (NAFLD) patients have not been reported.Objective. The aim of the present study was to assess visceral adipose tissue visfatin levels in NAFLD.Materials and methods. A total of 115 patients undergoing diagnostic laparoscopy were recruited in the study and categorized into two groups based on standard criteria for NAFLD. Visceral adipose tissue TNF-α, IL-6 and visfatin levels were measured by ELISA. Blood glucose, lipids, liver enzymes and non esterified fatty acids (NEFA) were estimated using standard procedures. Formalin fixed, Hematoxylene Eosin stained liver biopsy specimens were examined for the presence of steatosis and the degree of steatosis was ascertained as per Brunt’s classification.Results. The visceral visfatin level declined significantly (P < 0.001) in all groups of NAFLD as compared to non NAFLD group, while plasma NEFA level increased with progressive steatosis (P < 0.02). Significant increase in TNF a was observed in all groups of NAFLD, while IL-6 increased in NASH only.Conclusion. A significant decline in visceral adipose tissue visfatin level was found to be associated with degree of steatosis in NAFLD patients.