Hepatic Steatosis Grade Research Articles

Systemic redox imbalance in patients with nonalcoholic fatty liver disease

Oxidative stress is one of the major pathologic mechanisms for the progression of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the relationship between the extent of steatosis and oxidative stress parameters in patients with NAFLD. The data obtained from 122 patients with NAFLD and 106 healthy controls aged 20-60years with body mass index (BMI) ranging from 25 to 35kg/m2 . Abdominal ultrasonography was performed in participants in order to the grading of hepatic steatosis. Fasting blood samples and anthropometric measurements were collected for all study subjects. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC) and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) activities. Serum levels of liver enzymes (P<.0001) and MDA (P=.018), as well as erythrocyte SOD activity (P<.0001), were significantly higher in patients with NAFLD compared to healthy controls. Furthermore, patients with NAFLD had significantly lower serum TAC levels compared to healthy controls (P<.0001). No significant differences were observed in serum ox-LDL level and erythrocyte GPx activity between the groups. The probability of being NAFLD increased with increasing serum levels of MDA (P=.020) and SOD activity (P<.0001). In contrast, decreased serum TAC levels predicted the probability of being NAFLD (P<.0001). Increased extent of hepatic steatosis could be considered as a pathological mechanism for enhancing oxidative stress in patients with NAFLD, independent of obesity, and is exacerbated further in patients with more severe condition.

Cuantificación por resonancia magnética de esteatosis hepática y pancreática en hepatopatía crónica

AimTo compare pancreatic and hepatic steatosis quantified by proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) in patients with chronic liver disease. Material and MethodsThis cross-sectional study included 46 adult patients who underwent liver biopsy for chronic viral hepatitis (n=19) or other chronic non-alcoholic liver diseases (NALD) (n=27). Liver biopsy was used as the gold standard for diagnosing and grading hepatic steatosis. All patients underwent clinical evaluation and MRI with a multi-echo chemical shift-encoded (MECSE) gradient-echo sequence for liver and pancreas PDFF quantification. We used Spearman's correlation coefficient to determine the degree of association between hepatic PDFF and steatosis grade, and between pancreatic PDFF and steatosis grade and hepatic PDFF. To compare the chronic viral hepatitis group and the NALD group, we used t-tests for continuous or ordinal variables and chi-square tests for categorical variables. ResultsHepatic PDFF measurements correlated with steatosis grades (RS=0.875, p<0.001). Pancreatic PDFF correlated with hepatic steatosis grades (RS=0.573, p<0.001) and hepatic PDFF measurements (RS=0.536, p<0.001). In the subgroup of patients with chronic NALD, the correlations remained significant between pancreatic PDFF and hepatic PDFF (RS=0.632, p<0.001) and between pancreatic PDFF and liver steatosis (RS=0.608, p<0.001); however, in the subgroup of patients with viral hepatitis these correlations were no longer significant. ConclusionPancreatic fat deposition correlates with hepatic steatosis in patients with chronic NALD, but not in those with chronic viral hepatitis.

Effect of green coffee extract supplementation on serum adiponectin concentration and lipid profile in patients with non-alcoholic fatty liver disease: A randomized, controlled trial

ObjectivesThe current study evaluated the effects of green coffee extract (GCE) on serum lipid profile and adiponectin levels in patients with nonalcoholic fatty liver disease (NAFLD). DesignThis randomized, double-blind, placebo-controlled clinical trial was conducted on NAFLD patients aged 20–60 years and body mass index (BMI) of 25−35 kg/m2. SettingPatients were recruited from the Bahman poly-clinic (Neyshabur, Iran) between January and June 2016. InterventionsThe study subjects were randomly assigned to receive a daily dose of 400 mg GCE (n = 24) or placebo (n = 24) for eight weeks. Main outcome measuresSerum liver enzyme levels, lipid profile, adiponectin concentrations, and hepatic steatosis grade were measured for all patients at baseline and the end of the trial. ResultsGCE supplementation significantly reduced BMI [mean difference (MD): −0.57 and 95 % confidence interval (CI): −0.84 to −0.29, P < 0.001] and increased serum high-density lipoprotein cholesterol (MD: 7.06, 95 % CI: 0.25–13.87, P < 0.05) compared to the control group. Serum total cholesterol decreased significantly within the GCE group (MD: −13.33, 95 % CI: −26.04 to −0.61, P < 0.05). Triglyceride levels reduced significantly in GCE group compared to the placebo group (MD: -37.91; 95 % CI: −72.03 to −3.80; P = 0.03). However, this reduction was not significant when was further adjusted for mean changes in BMI and daily energy intake (MD: -23.43; 95 % CI: −70.92 to 24.06; P = 0.32). Hepatic steatosis grade, liver enzymes, and adiponectin levels did not show significant differences between the two groups after the intervention. ConclusionsGCE supplementation improved serum lipid profile and BMI in individuals with NAFLD. GCE may be useful in controlling NAFLD risk factors.

Association of Hepatic Global DNA Methylation and Serum One-Carbon Metabolites with Histological Severity in Patients with NAFLD.

Clinical relevance of global DNA methylation and one-carbon metabolite levels with histological severity remains uncertain in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate hepatic global DNA methylation and serum one-carbon metabolite concentrations in patients with NAFLD and the possible associations of these parameters with liver histology. Liver biopsies from 18 control participants and 47 patients with NAFLD were evaluated. The hepatic global DNA methylation level was significantly lower in the NAFLD group than in the control group among participants with overweight. Participants with moderate inflammation and mild fibrosis had significantly lower levels of global DNA methylation than those without these characteristics. Participants with borderline nonalcoholic steatohepatitis had significantly lower global DNA methylation levels than controls. The hepatic global DNA methylation level tended to decrease with the increasing hepatic inflammation grade and disease progression. The NAFLD group had a significantly higher serum homocysteine concentration than the control group among participants with overweight. This level tended to increase with increasinghepatic steatosis grade and disease progression. Patients with NAFLD exhibited lower hepatic levels of global DNA methylation and elevated serum homocysteine concentrations, which are associated with the histological severity of NAFLD.

Correlation of the grade of hepatic steatosis between controlled attenuation parameter and ultrasound in patients with fatty liver: a multi-center retrospective cohort study.

Background/AimsThe controlled attenuation parameter (CAP), based on transient elastography, is widely used for noninvasive assessment of the degree of hepatic steatosis (HS). We investigated the correlation of the degree HS between CAP and ultrasound (US) in patients with HS.MethodsIn total, 986 patients with US-based HS who underwent transient elastography within 1 month were evaluated. The US-based grade of HS was categorized as mild (grade 1), moderate (grade 2), or severe (grade 3).ResultsThe CAP was significantly correlated with the US-based grade of HS (r = 0.458, p < 0.001). The median CAP value of each US-based HS grade showed a positive correlation with grade (271.1, 303.7, and 326.7 dB/m for grades 1, 2, and 3). In a multivariate analysis, the US-based HS grade, body mass index, serum albumin, alanine aminotransferase, and total cholesterol, and liver stiffness were all significantly correlated with the CAP value (all p < 0.05). The areas under the receiver operating characteristic curves for grade 2 to 3 and grade 3 HS were 0.749 (95% confidence interval [CI], 0.714 to 0.784) and 0.738 (95% CI, 0.704 to 0.772). The optimal cut-off CAP values to maximize the sum of the sensitivity and specificity for grade 2 to 3 and grade 3 HS were 284.5 dB/m (sensitivity 78.6%, specificity 61.7%) and 298.5 dB/m (sensitivity 84.6%, specificity 55.6%).ConclusionsThe correlation of the degree of HS between CAP and US was significantly high in patients with HS, and the optimal cut-off CAP values for grade 2 to 3 and grade 3 HS were 284.5 and 298.5 dB/m.

Nonalkolik yağlı karaciğer hastalığı olan bireylerde Tp-e intervali ve Tp-e/qt oranı

Aim: Ventricular repolarization is assessed using the Tp-e interval and QT interval corrected by the heart rate (QTc) via an electrocardiogram (ECG). Prolonged Tp-e/QTc is related with an increased risk of arrhythmias and cardiac mortality. As there have been few reports regarding the effects of NAFLD on ventricular repolarization, we aimed to appraise the assessment of Tp-e interval and Tp-e/QT ratio in patients with NAFLD. Material and Methods: Totally 97 patients with NAFLD and 77 control subjects were enrolled in our study. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Results: Heart rate was similar between groups (74.8 ± 10.1 vs. 75.7 ± 11.7; p=0.598). QT interval (396.0 ± 34.2 vs. 384.6 ± 30.7; p=0.023) and QTc interval (403.6 ± 34.8 vs. 399.9 ± 36.3; p=0.027), Tp-e interval (100.4 ± 13.6 vs. 91.4 ± 13.4; p&amp;lt;0.001) , Tp-e/QT ratio (0.25 ± 0.03 vs. 0.23 ± 0.03; p=0.003) and Tp-e/QTc ratio (0.23 ± 0.03 vs. 0.21 ± 0.03; p=0.002) were significantly different between groups. There was significant correlation between Tp-e interval (r= 0.328, p&amp;lt;0.001) and Tp-e/QTc ratio and hepatic steatosis grade (r= 0.237, p=0.002). Conclusion: Tp-e interval, QT interval, QTc interval, Tp-e/QT and Tp-e/QTc ratios were prolonged in patients with NAFLD. NAFLD is found an independent factor for increased Tp-e/QT ratio. This is the first study that investigated the Tp-e interval and Tp-e/QT parameters in patients with NAFLD.

Volumetric Liver Fat Fraction Determines Grade of Steatosis More Accurately Than Controlled Attenuation Parameter in Patients With Nonalcoholic Fatty Liver Disease

HepaFat-Scan is a magnetic resonance imaging-based method for quantification of hepatic steatosis by volumetric liver fat fraction (VLFF) measurement. We aimed to validate VLFF and to compare it with controlled attenuation parameter (CAP) for determination of hepatic steatosis grade in patients with NAFLD, using histopathology and stereologic analyses of biopsies as the reference standard. We performed a prospective study of consecutive adults with NAFLD who were scheduled for a liver biopsy at a tertiary hospital in Malaysia. Patients underwent VLFF and CAP measurements on the same day as their liver biopsy. Histopathology analyses of liver biopsy specimens were reported according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Stereologic analysis was performed using grid-point counting method combined with the Delesse principle. We analyzed data from 97 patients (mean age 57.0 ± 10.1 years; 44.33% male; 91.8% obese; 95.9% centrally obese). Based on histopathology analysis, the area under receiver operating characteristic curve (AUROC) for VLFF in detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.65 (P < .001). Based on stereological analysis, the AUROC for VLFF for detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.63, (P = .002); for identification of steatosis grade S3, the AUROC for VLFF was 0.92 and for CAP the AUROC was 0.68 (P < .001). In a prospective study of patients with NAFLD undergoing liver biopsy analysis, we found VLFF to more accurately determine grade of hepatic steatosis than CAP.

Reproducibility of ultrasound attenuation imaging for the noninvasive evaluation of hepatic steatosis.

PurposeThe purpose of this study was to evaluate the intra-observer reproducibility of ultrasound attenuation imaging (ATI) for the noninvasive assessment of hepatic steatosis in patients with suspected hepatic steatosis and the inter-observer reproducibility in asymptomatic volunteers.MethodsThis prospective study was approved by our institutional review board and informed consent was obtained from all patients. In group 1, composed of patients with suspected hepatic steatosis (n=143), one abdominal radiologist performed gray-scale ultrasonography and two sessions of ATI. In group 2, composed of healthy volunteers (n=18), three independent sessions of ATI were performed by three abdominal radiologists. The visual degree of hepatic steatosis in all study subjects was graded on a 4-point scale by two independent reviewers using gray-scale ultrasonography. Thereafter, the attenuation coefficient (AC) was correlated with the degree of hepatic steatosis using Spearman rank correlation analysis. Intra-class correlation coefficients (ICCs) were used to assess the intra-observer (group 1) and inter-observer reproducibility (group 2) of ATI measurements.ResultsFor the intra-observer reproducibility of ATI, the ICC was 0.929 (95% confidence interval [CI], 0.901 to 0.949), and the coefficient of variation was 7.1%. Inter-observer reproducibility of ATI measurements showed an ICC of 0.792 (95% CI, 0.549 to 0.916). The AC showed a significant correlation with the visual grade of hepatic steatosis for both reviewers (rho, 0.780 and 0.695; P<0.001, respectively).ConclusionATI showed high intra- and inter-observer reproducibility in the assessment of hepatic steatosis.

The clinical usefulness of elastography in the evaluation of nonalcoholic fatty liver disease patients: A biopsy-controlled study.

We aimed at determination of the usefulness of elastography [acoustic radiation force impulse (ARFI) and FibroScan] for evaluation of nonalcoholic fatty liver disease (NAFLD) patients. A prospective cross-sectional study included 60 biopsy-proven NAFLD patients (mean age: 45 years) was carried out. All patients were subjected to lab works, liver biopsy, and measurement of liver stiffness by ARFI and FibroScan and steatosis by controlled attenuation parameter (CAP). CAP measurements were adjusted for the presence of NAFLD and presence or absence of diabetes and according to BMI. Linear regression analysis showed that CAP is an independent predictor for significant hepatic steatosis (P<0.001). No significant difference was found in diagnostic accuracy between adjusted and nonadjusted CAP values for diagnosis of mild (>S1) or significant (>S2) hepatic steatosis (P=0.17 and 0.29 respectively). The median ARFI velocities for F1, F2, F3, and F4 were 0.92, 1.08, 1.07, and 2.58 m/s, respectively. Although there was an overall significant increase in ARFI values across the fibrosis grades (P<0.04), the difference in ARFI values was only significant between fibrosis grades F1 and F4 (P=0.02). Elastography is a promising noninvasive tool for diagnosis and grading of hepatic steatosis and fibrosis in patients with NAFLD/nonalcoholic steatohepatitis with good sensitivity and specificity, especially in moderate to marked grades.

Quick assessment with controlled attenuation parameter for hepatic steatosis in children based on MRI-PDFF as the gold standard

BackgroundControlled attenuation parameter (CAP) is a recently introduced, non-invasive and quantitative method to evaluate hepatic steatosis demonstrated in adults, but limited in obesity and not well evaluated in children. The aim of this study was to investigate the diagnostic performance for assessing hepatic steatosis grades using CAP in children based on MR proton density fat fraction (PDFF).MethodsChildren evaluated for non-alcoholic fatty liver disease (NAFLD) who were assessed for PDFF and CAP were enrolled retrospectively. Hepatic steatosis grades 0–3 were classified according to PDFF using cutoff values of 6, 17.5, and 23.3%. Subgroup analyses were performed in non-obese and obese groups using the 95th percentile body mass index (BMI) as a cutoff and BMI30 group when BMI > 30 kg/m2. Pearson’s correlations between variables were also analyzed.ResultsIn a total of 86 children, there were 53 in the obese group including 17 of the BMI30 group. CAP demonstrated 98.7% sensitivity and 80% specificity for diagnosing grades 1–3 vs. grade 0 using a cutoff value of 241 dB/m (area under the curve = 0.941, p < 0.001). The diagnostic performance for higher steatosis grades was suboptimal. CAP correlated with abdominal wall thickness in both obese (r = 0.549, p = 0.001) and non-obese (r = 0.386, p = 0.004) groups and did not correlate with PDFF in BMI30 group.ConclusionIn children with NAFLD, CAP showed excellent diagnostic performance for differentiating presence and absence of hepatic steatosis using a cutoff value of 241 dB/m. However, CAP was limited in evaluating grades of steatosis, especially in children with BMI > 30 kg/m2.

Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: a meta-analysis.

To systematically review studies about the diagnostic accuracy of magnetic resonance imaging proton density fat fraction (MRI-PDFF) in the classification of hepatic steatosis grade in patients with non-alcoholic fatty liver disease (NAFLD). Areas under the summary receiver operating characteristic curves (AUROC), sensitivity, specificity, overall diagnostic odds ratio (DOR), diagnostic score, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) for MRI-PDFF in classification of steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were compared and analyzed. A total of 6 studies were included in this meta-analysis (n= 635). The summary AUROC values of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 0.98, 0.91, and 0.90, respectively. Pooled sensitivity and specificity of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 0.93 and 0.94, 0.74 and 0.90, and 0.74 and 0.87, respectively. Summary +LR and -LR of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 16.21 (95%CI, 4.72-55.67) and 0.08 (95%CI, 0.04-0.15), 7.19 (95%CI, 5.04-10.26) and 0.29 (95%CI, 0.22-0.38), and 5.89 (95%CI, 4.27-8.13) and 0.29 (95%CI, 0.21-0.41), respectively. Our meta-analysis suggests that MRI-PDFF has excellent diagnostic value for assessment of hepatic fat content and classification of histologic steatosis in patients with NAFLD. • MRI-PDFF has significant diagnostic value for hepatic steatosis in patients with NAFLD. • MRI-PDFF may be used to classify grade of hepatic steatosis with high sensitivity and specificity.

Association of sex hormone-binding globulin with nonalcoholic fatty liver disease in Chinese adults

BackgroundSex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults.MethodsWe conducted a community-based, cross-sectional study in China involving 2912 participants aged 40–75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis.ResultsSerum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4–56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6–83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p < 0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p < 0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides.ConclusionsThese results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults.

Ultrasonic Adaptive Sound Speed Estimation for the Diagnosis and Quantification of Hepatic Steatosis: A Pilot Study.

To evaluate the ability of a new ultrasound (US) method based on sound speed estimation (SSE) with respect to the detection, quantification, and grading of hepatic steatosis using magnetic resonance (MR) proton density fat fraction (PDFF) as the reference standard and to calculate one US fat index based on the patient's SSE. This study received local IRB approval. Written informed consent was obtained from patients. We consecutively included N = 50 patients as the training cohort and a further N = 50 as the validation cohort who underwent both SSE and abdominal MR. Hepatic steatosis was classified according to MR-PDFF cutoffs as: S0 ≤ 6.5 %, S1 6.5 to 16.5 %, S2 16.5 to 22 %, S3 ≥ 22 %. Receiver operating curve analysis was performed to evaluate the diagnostic performance of SSE in the diagnosis of steatosis (S1-S3). Based on the optimal data fit derived from our study, we proposed a correspondence between the MR-PDFF and a US fat index. Coefficient of determination R2 was used to evaluate fit quality and was considered robust when R2 > 0.6. The training and validation cohorts presented mean SSE values of 1.570 ± 0.026 and 1.568 ± 0.023 mm/µs for S0and 1.521 ± 0.031 and 1.514 ± 0.019 mm/µs for S1-S3 (p < 0.01) patients, respectively. An SSE threshold of ≤ 1.537 mm/µs had a sensitivity of 80 % and a specificity of 85.7 % in the diagnosis of steatosis (S1-S3) in the training cohort. Robust correspondence between MR-PDFF and the US fat index was found both for the training (R2 = 0.73) and the validation cohort (R2 = 0.76). SSE can be used to detect, quantify and grade liver steatosis and to calculate a US fat index.

Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty liver disease.

We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non-obese and obese nonalcoholic fatty liver disease. A cross-sectional study of 664 Asian subjects (mean age 53.1years; men 50.3%) with biopsy-proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25kg/m2 ) and non-obese (body mass index <25kg/m2 ). Observations in subjects with non-obese nonalcoholic fatty liver disease were in between non-obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non-obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high-density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non-obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non-obese nonalcoholic fatty liver disease. While there were a few phenotypic differences from obese subjects, non-obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese nonalcoholic fatty liver disease advances to more severe disease.

Relationship between Serum Cytokeratin-18, Control Attenuation Parameter, NAFLD Fibrosis Score, and Liver Steatosis in Nonalcoholic Fatty Liver Disease.

Backgrounds The aim of this study was to appraise the relationship between serum fragmented cytokeratin-18(CK-18), controlled attenuation parameter (CAP), and liver steatosis assessed by ultrasound (US) in nonalcoholic fatty liver disease (NAFLD) patients. Methods Patients who underwent abdominal US were recruited, followed with measurement of CAP using Fibroscan® and serum fragmented CK-18 using enzyme-linked immunosorbent assay. The degree of liver steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). Results A total of 109 patients were included in our study. CAP and fragmented CK-18 level were significantly correlated with liver steatosis grade with rs = 0.56 and 0.68, p=0.001, respectively. NAFLD Fibrosis Score was poorly correlated with liver steatosis grade (rs=-0.096, p=0.318). Using fragmented CK-18 level, area under receiver operating characteristic (AUROC) curves for S≥2 and S≥3 were excellent (0.82 and 0.84, respectively). Using CAP, AUROC curves for detection of S≥2 and S≥3 were good (0.76, 0.77, respectively). We also proposed cut-off value of CAP to detect S≥2 and S≥3 to be 263 and 319db/m, respectively, and fragmented CK-18 level to detect S≥2 and S≥3 (194 and 294 U/L, respectively). Conclusions Both the fragmented CK-18 level and the CAP, but not NAFLD Fibrosis Score, were well correlated with hepatic steatosis grade as assessed by US.

PNPLA3 rs738409 Polymorphism Predicts Development and Severity of Hepatic Steatosis but Not Metabolic Syndrome in Celiac Disease.

Metabolic syndrome (MS) and hepatic steatosis (HS) have been described in patients with celiac disease (CD) after starting a gluten-free diet (GFD), but data on predictive factors for these conditions are scarce. Recently, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 has been identified as a key factor for HS development in the general population. The aim of the study was to evaluate the role of PNPLA3 rs738409 in the development of MS and HS in CD patients after starting GFD. Between June 2014 and September 2016, we consecutively enrolled CD patients with HS, while those without steatosis served as a control group. All patients underwent anthropometric and serologic investigations, ultrasonography (US) to assess the degree and severity of HS, and genotyping of the PNPLA3 rs738409 polymorphism. Finally, 370 subjects were enrolled (136 with and 234 without HS). At genotyping assays, the CC genotype was found in 194 subjects (52.4%), the CG genotype in 138 subjects (37.3%), and the GG genotype in 38 subjects (10.2%). At binary logistic regression, only CG and GG alleles were predictive for the development of HS (odds ratio (OR) 1.97; p < 0.01 for CG and OR 6.9; p < 0.001 for GG). Body mass index (BMI) (OR 3.8; p < 0.001) and waist circumference (OR 2.8; p = 0.03) at CD diagnosis were the only independent factors for the development of MS. Intergroup comparisons showed that the severe grade of HS was more frequently observed in GG than in CC carriers (74% vs. 11.3%, p < 0.001, OR 21.8). PNPLA3 CG and GG carriers with CD have a higher susceptibility to hepatic steatosis, but not to metabolic syndrome. Moreover, patients with GG alleles display more severe forms of HS based on ultrasound.

Reader agreement and accuracy of ultrasound features for hepatic steatosis.

The purpose of the study is to assess the reader agreement and accuracy of eight ultrasound imaging features for classifying hepatic steatosis in adults with known or suspected hepatic steatosis. This was an IRB-approved, HIPAA-compliant prospective study of adult patients with known or suspected hepatic steatosis. All patients signed written informed consent. Ultrasound images (Siemens S3000, 6C1HD, and 4C1 transducers) were acquired by experienced sonographers following a standard protocol. Eight readers independently graded eight features and their overall impression of hepatic steatosis on ordinal scales using an electronic case report form. Duplicated images from the 6C1HD transducer were read twice to assess intra-reader agreement. Intra-reader, inter-transducer, and inter-reader agreement were assessed using intraclass correlation coefficients (ICC). Features with the highest intra-reader agreement were selected as predictors for dichotomized histological steatosis using Classification and Regression Tree (CART) analysis, and the accuracy of the decision rule was compared to the accuracy of the radiologists' overall impression. 45 patients (18 males, 27 females; mean age 56 ± 12years) scanned from September 2015 to July 2016 were included. Mean intra-reader ICCs ranged from 0.430 to 0.777, inter-transducer ICCs ranged from 0.228 to 0.640, and inter-reader ICCs ranged from 0.014 to 0.561. The CART decision rule selected only large hepatic vein blurring and achieved similar accuracy to the overall impression (74% to 75% and 68% to 72%, respectively). Large hepatic vein blurring, liver-kidney contrast, and overall impression provided the highest reader agreement. Large hepatic vein blurring may provide the highest classification accuracy for dichotomized grading of hepatic steatosis.

Extruded sorghum (Sorghum bicolor L.) reduces metabolic risk of hepatic steatosis in obese rats consuming a high fat diet

The study investigated the effect of extruded sorghum flour (ESF) in a high fat diet (HFD) on biometric measurements and hepatic lipogenesis. Male Wistar rats were fed a normal diet (AIN-93M), HFD, HFD plus ESF replacing 50% cellulose and 100% corn starch (HFDS50), or HFD plus ESF replacing 100% cellulose and 100% corn starch (HFDS100) for eight weeks. ESF reduced the body mass index and liver weight of obese rats. Additionally, ESF reduced hepatic lipogenesis by increasing adiponectin 2 receptor gene expression and gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα), while reducing the gene expression of sterol regulatory element-binding transcription factor 1. Molecular docking analysis revealed the affinity of ESF compounds (luteolinidin, apigeninidin, 5-methoxy-luteolinidin, and 7-methoxy-apigeninidin) with the PPAR-α receptor. Histological analysis confirmed the decreased grade of hepatic steatosis in obese rats. These data indicate the potential of ESF to reduce metabolic risk of hepatic steatosis associated with lipogenesis and obesity.

Can the same controlled attenuation parameter cut-offs be used for M and XL probes for diagnosing hepatic steatosis?

There are limited studies on controlled attenuation parameter (CAP) using Fibroscan XL probe for the diagnosis of hepatic steatosis grade. The aim of this study was to determine whether previously defined optimal cut-offs for CAP using the M probe could be applied for the XL probe. Adult patients with chronic liver disease who had a liver biopsy and examination with both the M and XL probes were included. Previously defined optimal cut-offs for CAP using the M probe were used for the diagnosis of steatosis grades ≥S1, ≥S2, and S3 (248, 268, and 280dB/m, respectively). Data for 180 patients were analyzed (mean age 53.7±10.8years; central obesity 84.5%; non-alcoholic fatty liver disease 86.7%). The distribution of steatosis grades was S0, 9.4%; S1, 28.3%; S2, 43.9%, and S3, 18.3%. The sensitivity, specificity, positive predictive value, and negative predictive value of CAP using the M/XL probe for the diagnosis of steatosis grade ≥S1 was 93.9%/93.3%, 58.8%/58.8%, 95.6%/95.6%, and 50.0%/47.6%, respectively. These values were 94.6%/94.6%, 41.2%/44.1%, 72.6%/73.6%, and 82.4%/83.3%, respectively, for ≥S2, and 87.9%/87.9%, 27.2%/27.9%, 21.3%/21.5%, and 90.9%/91.1%, respectively, for S3. The same cut-off values for CAP may be used for the M and XL probes for the diagnosis of hepatic steatosis grade.

Return-to-health effect of modern combined antiretroviral therapy potentially predisposes HIV patients to hepatic steatosis.

Prevalence and risk factors for hepatic steatosis (HS) in the human immunodeficiency virus (HIV)-positive population of western countries are controversially discussed and potentially confounded by coinfection with viral hepatitis. Significant HS (more than 10% of hepatocytes) can be accurately assessed using controlled attenuation parameter (CAP) determination. Aim of this study was to assess prevalence and factors associated with significant HS in HIV monoinfected patients.A total of 364 HIV-infected patients (289 monoinfected) were included in this prospective, cross-sectional study. All patients underwent CAP determination. Steatosis was classified as S1 (significant steatosis) with CAP > 238 dB/m, S2 with CAP > 260 dB/m, and S3 with CAP > 292 dB/m. Multivariable logistic regression analyses were performed to assess the factors associated with HS in this cohort.Significant HS was detected in 118 monoinfected patients (149 in the total cohort). In the total cohort as well as in the monoinfected patients alone, HS grade distribution showed a similar pattern (S1:29%, S2:34%, and S3:37%). Interestingly, patients with HS had a longer history of HIV infection and combined antiretroviral therapy (cART). Interalia, age, gender, ethnicity, and metabolic factors were strongly associated with HS, while body mass index (BMI), triglyceride, and glycated hemoglobin (HbA1c) levels were independently associated with significant HS.HS is highly prevalent among HIV monoinfected patients. Although metabolic risk factors, such as obesity and poorly controlled diabetes, are independently associated with HS in HIV monoinfected patients, cART and control of HIV seem to play an indirect role in the development of HS, probably through the return-to-health effect.