Severe Steatosis Research Articles

Comparison of Complications in Patients with Ductal Cholangiocarcinoma (CCC) and Patients with Colorectal Liver Metastases (CRLMs) After Portal Vein Embolization (PVE): A Matched Cohort Study.

To compare complications in patients with cholangiocarcinoma (CCC) and patients with colorectal liver metastases (CRLMs) after portal vein embolization (PVE) and to identify possible predictive factors. Retrospective analysis of consecutive patients, who underwent PVE between July 2011 and March 2020. The study groups were matched for sex and age. Multivariable analysis was performed for the endpoints of complications categorized according for their respective effect on surgical treatment: "Minor" complications had no effect on subsequent surgical treatment, while "intermediate" and "severe" complications delayed or prevented surgery. A total of 160 patients with either CCC (n = 80) or CRLMs (n = 80) were included: 34/160 experienced complications: 27 (CCC: 21; CRLMs: 6) "minor", 4 (CCC: 3; CRLMs: 1) "intermediate", and 3 (CCC: 2; CRLMs: 1) "severe" complications respectively (p = .01). Patients with CCC received a biliary drainage 5days on average before PVE. Baseline bilirubin levels were 1.1mg/dl in CCC patients and 0.55mg/dl in CRLMs patients (p < .01). Postinterventional infections were more common in CCC patients. The preintervention future liver remnant volume (odds ratio (OR) 0.93; 95% confidence interval (CI) 0.88-0.99; p = .02), body mass index (OR 1.19; 95% CI 1.04-1.36; p = .01), age (OR 0,91; 95% CI 0.84-0.99; p = .01), chemotherapy before PVE (OR 0.03; 95% CI 0.01-0.23; p < .01) and severe liver steatosis (OR 29.52; 95% CI 1.87-467,13; p = .02) were the only significant predictive factors for the occurrence of (minor) complications. PVE can be performed in CCC patients with prior biliary drainage, with similar procedural safety as in patients with CRLMs.

Correlation between controlled attenuation parameter values with SYNTAX score in patients with significant coronary artery disease

Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver disease, with coronary artery disease (CAD) as the main cause of death in NAFLD patients. However, correlation between the severity of liver steatosis and coronary atherosclerosis is yet to be understood. Here we aim to explore the correlation between controlled attenuation parameter (CAP) values and SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in adult patients with significant CAD, defined as ≥ 50% stenosis of the left main coronary artery, or ≥ 70% stenosis of the other major coronary arteries. A cross-sectional study was conducted on 124 adult patients with significant CAD who underwent coronary angiography. Transient elastography with CAP was used to assess liver steatosis severity, resulting in a mean CAP value of 256.5 ± 47.3 dB/m, with 52.5% subjects had significant steatosis (CAP value of ≥ 248 dB/m). Median SYNTAX score was 22. A statistically significant correlation was observed between CAP value and SYNTAX score (r = 0.245, p < 0.0001). The correlation was more pronounced in patients with prior history of PCI (r = 0.389, p = 0.037). Patients with high-risk SYNTAX score (> 32) had the highest CAP value (285.4 ± 42.6 dB/m), and it was significantly higher than those with low-risk SYNTAX score (0–22), with a mean difference of 38.76 dB/m (p = 0.006). Patients with significant liver steatosis should undergo periodic CAD assessment and lifestyle modification, especially those with severe liver steatosis.

Value of Zonulin as a Diagnostic and Prognostic Marker in Patients with Nonalcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple fat accumulation in the hepatocytes (hepatic steatosis), to liver inflammation and hepatocytes injury (nonalcoholic steatohepatitis, NASH) with increasing levels of fibrosis to cirrhosis and hepatocellular carcinoma (HCC). The gut microbiota is involved in the occurrence and development of chronic liver diseases. Zonulin is considered a marker of intestinal permeability. Aim and Objectives to study the value of zonulin as a diagnostic and prognostic marker in different degrees of Non-alcoholic fatty liver disease (Steatosis, Steatohepatitis, Cirrhosis) in patients with and without Diabetes Mellitus. Subjects and Methods This was Case control study, was conducted in Ain-Shams University Hospitals Internal medicine&amp; Gastroenterology department and bariatric surgery unit over 60 subjects divided into 3 groups:(Group A): 20 Patients have mild NASH, (Group B): 20 Patients have moderate to severe NASH, (Group C): 20 Healthy controls, during a period 1 year. Result There was high statistically significant difference between the studied groups as regard Zonulin concentration. Conclusion serum zonulin concentration is increased in patients with NAFLD and correlates with the severity of steatosis. However, the cross-sectional design of our study precludes the establishment of causal or temporal relationships between increased zonulin concentrations and severity of steatosis and the presence of NASH. Follow up studies may be helpful in elucidating the cause-and effect relations and the underlying mechanisms.

Role of Lipocalin-2 Levels in Non-Alcoholic Fatty Pancreatic Disease and its Association with Non-Alcoholic Fatty Liver Disease

Abstract Background Lipocalin-2 (LCN2) is a 25-kDa secretory protein with great importance as a sensitive and specific screening and diagnostic biomarker for hepatic inflammation, acute hepatic injury, hepatic cancer, and radiation-induced early phase hepatic damage and lipid abnormalities. However, little is known about LCN2's functions in the homeostasis and metabolism of hepatic lipids or in the development of steatosis as well as its actual role in the event of inflammation. Aim and Objectives To establish a correlation between the levels of lipocalin as a useful biomarker with increasing severity of steatosis in NAFLD and NAFPD patients. Subjects and Methods This was observational prospective case–control study, was conducted at Hepatology Unit of Ain Shams University Hospital on 50 patients diagnosed with NAFPD and 50 healthy age and sex-matched volunteers without NAFPD during a period of 6 months. All patients were subjected to; Full history taking and thorough clinical examination, Anthropometric measurements, Laboratory investigations, and abdominal ultrasonography. Result There was a significant Positive correlation between Lipocalin 2, BMI, LDL (mg/dL), Cholesterol (mg/dL), Insulin (μU/mL) and HOMA-IR in patient group(P-value ≤ 0.001), Conclusion; lipocalin-2 is a good blood biomarker for detection of hepatic and Pancreatic steatosis. The lipocalin levels increase with increasing severity of steatosis. In addition to this, lipocalin will be useful for early diagnosis of NAFLD, NAFPD and convenient to do with other blood tests. The early intervention may prevent high morbidity and mortality and to manage the disease properly.

Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation

BackgroundMetabolic associated fatty liver disease (MAFLD), a prevalent liver disorder affecting one-third of the global population, encompasses a spectrum ranging from fatty liver to severe hepatic steatosis. Both genetic and lifestyle factors, particularly diet and nutrition, contribute to its etiology. Folate deficiency, a frequently encountered type of malnutrition, has been associated with the pathogenesis of MAFLD and shown to impact lipid deposition. However, the underlying mechanisms of this relationship remain incompletely understood. We investigated the impact of disturbed folate-mediated one-carbon metabolism (OCM) on hepatic lipid metabolism both in vitro using human hepatoma cells and in vivo using transgenic fluorescent zebrafish displaying extent-, stage-, and duration-controllable folate deficiency upon induction.ResultsDisturbed folate-mediated one-carbon metabolism, either by inducing folate deficiency or adding anti-folate drug, compromises autophagy and causes lipid accumulation in liver cells. Disturbed folate status down-regulates cathepsin L, a key enzyme involved in autophagy, through inhibiting mTOR signaling. Interfered mitochondrial biology, including mitochondria relocation and increased fusion-fission dynamics, also occurs in folate-deficient hepatocytes. Folate supplementation effectively mitigated the impaired autophagy and lipid accumulation caused by the inhibition of cathepsin L activity, even when the inhibition was not directly related to folate deficiency.ConclusionsDisruption of folate-mediated OCM diminishes cathepsin L expression and impedes autophagy via mTOR signaling, leading to lipid accumulation within hepatocytes. These findings underscore the crucial role of folate in modulating autophagic processes and regulating lipid metabolism in the liver.

Regional fat distribution and hepatic fibrosis and steatosis severity in patients with nonalcoholic fatty liver disease and type 2 diabetes.

Epidemiologic findings suggest that measures of body fat distribution predict health outcomes independent of the overall body fat assessed by body mass index (BMI). This study aimed to evaluate the associations of overall and regional body fat with the severity of hepatic steatosis and fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease. Bioelectric impedance analysis and two newly developed anthropometric indices, namely, A Body Shape Index (ABSI) and Body Roundness Index (BRI), were used to estimate the body fat. Based on fibroscan parameters, significant hepatic fibrosis and severe steatosis were defined as ≥F2 and >66%, respectively. Higher total body fat (odds ratio [OR] 1.107, 95% confidence intervals (CI) 1.038-1.182, p=0.002), trunk fat (OR 1.136, 95% CI 1.034-1.248, p=0.008) and leg fat (OR 1.381, 95% CI 1.139-1.674, p=0.001) were associated with liver fibrosis. However, in contrast to the total body fat (OR 1.088, 95% CI 1.017-1.164, p=0.014) and leg fat (OR 1.317, 95% CI 1.066-1.628, p=0.011), the trunk fat was not associated with severe hepatic steatosis. BRI performed better than trunk, leg and total body fat in predicting hepatic steatosis (OR 2.186, 95% CI 1.370-3.487, p=0.001) and fibrosis (OR 2.132, 95% CI 1.419-3.204, p<0.001). Moreover, the trunk to leg fat ratio and ABSI were not independent predictors of either steatosis or fibrosis (p>0.05). BRI revealed a superior predictive ability for identifying the degree of hepatic steatosis and stiffness than other obesity indices. Additionally, higher levels of adiposity in the trunk, legs, and overall body were linked to an increased risk of developing liver fibrosis. Although trunk fat did not show an association with severe hepatic steatosis, an increase in leg and total fat was related to liver steatosis.

Revisiting the Hepatorenal Index in the Quantification of Hepatic Steatosis: How it is done and the utility.

Twenty-three peer-reviewed articles on HRI measurements published between 2018 through 2023 were reviewed, and 11 were selected based on common subjects. The search terms included "hepatorenal index," "HRI," "HRI ultrasound," "hepatorenal ultrasound index," and "HRI ultrasound measurement."Three common subject areas were identified in the literature and synthesized down to 11 articles. The common subjects identified were HRI technique, HRI limitations, and HRI diagnostic accuracy. The matrix provided a quick overview of the general information in each piece, aiding in the paper's overall organization. Thirteen articles were rejected as not relevant or out of date. The research question leading this review was, "What does the literature say about the value of HRI in determining moderate to severe hepatic steatosis?" The literature revealed that HRI could be valuable in determining moderate to severe hepatic steatosis. HRI could not accurately determine normal or mild steatosis and has several limitations. HRI is a more objective method for determining the degree of hepatic steatosis compared with traditional B-mode ultrasound scoring and does not require additional or specialized equipment. Many studies excluded patients with various liver diseases, which may not make HRI a practical tool for clinical usefulness. Further studies should be conducted with larger patient cohorts, a greater degree of hepatic steatosis, and determine specific standardized cutoff values.

Malnutrition-Related Liver Steatosis, CONUT Score and Poor Clinical Outcomes in an Internal Medicine Department.

Fatty liver disease has been identified as a marker of malnutrition in different clinical settings. Recently, the COntrolling NUTritional status score (CONUT score) emerged as a promising tool for malnutrition assessment. Our aim was to evaluate short-term outcomes among patients with malnutrition-related liver steatosis in an Internal Medicine department. Furthermore, we evaluated the association of the CONUT score with malnutrition-related liver steatosis. Data from 247 patients hospitalized in an Internal Medicine department were retrospectively collected. The study population was stratified into three groups based on hepatic radiodensity assessed with computed tomography: mild steatosis (≥56.1 HU), moderate steatosis (between 49.7 and 56 HU), and severe steatosis (≤49.6 HU). We then calculated the CONUT score. Severe steatosis patients had higher in-hospital mortality (18.2 vs. 15.5%) and longer in-hospital stays compared with the mild steatosis group (length of in-hospital stay longer than 12 days: 45% vs. 40%). Logistic regression analysis showed that severe steatosis was not significantly associated with in-hospital all-cause death, while a high CONUT score was an independent risk factor for sepsis. We found an independent relationship between malnutrition-associated liver steatosis and the CONUT score. These results identified the CONUT score as a tool for nutritional assessment of hospitalized patients.

Influence of age, body mass index and gender on sonographic indicators of the liver in patients with metabolic dysfunction-associated steatotic liver disease

Background. The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing along with the increasing prevalence of obesity. There are close relationships between these two pathologies due to the functioning of adipose tissue as an endocrine organ with a complex influence on various metabolic processes. It is known that premenopausal women are less prone to fatty liver disease than men. The aim was to study the influence of gender, body mass index (BMI) and age on sonographic indicators and the degree of liver steatosis in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Ninety-two patients with MASLD were included in the study, 48 women and 44 men. Inclusion criterion was metabolic dysfunction-associated steatotic liver disease, exclusion criteria were any non-metabolic factors of chronic diffuse liver disease. Patients were divided into groups by gender and age. Women were divided by age according to the presence and absence of menopause, men were divided into groups below and above 45 years — the conventional age of the beginning of the decline in gonadotropic function. The analysis of structural changes of the liver, namely the assessment of the size, contours, structure, echogenicity, and visualization of blood vessels in the B-mode was carried out with the help of ultrasound examination on Toshiba Xario 660 (Japan). The degree of steatosis was assessed by the controlled attenuation parameter. Results. In men, the right, left and caudate liver lobes were significantly larger (p &lt; 0.05) than in women, which is due to the higher weight of men in the absence of a difference in the BMI. There was no significant difference between men and women in degree of steatosis (p &gt; 0.05). A moderate positive correlation (r = 0.63) was found between BMI and the controlled attenuation parameter; in women, there was no connection between these indicators. Analysis of correlations in women of different ages, divided by the presence of menopause, found that before menopause, there was no dependence of steatosis indicators on BMI, while with the onset of menopause, the coefficient of correlation between these indicators was 0.39 (р &lt; 0.02). Conclusions. No significant difference was found between the frequency of various degrees of steatosis in MASLD according to the controlled attenuation parameter in men and women. There was a dependence of the severity of liver steatosis on the BMI in men, the dependence of steatosis on the body mass index in women was manifested starting from the menopause period, which suggests the protective role of female sex hormones.

Value of zonulin as a diagnostic and prognostic marker in different degrees of nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is a group of hepatic disorders ranging between simple form of accumulation of fat in hepatocytes (hepatic steatosis) and inflammation of liver internal tissues and injury of hepatocytes that is known as nonalcoholic steatohepatitis (NASH) with increasing levels of fibrosis and cirrhosis and hepatocellular carcinoma (HCC). The composition of one’s gut microbiota has a role in both the onset and progression of chronic liver disorders. One indicator of intestinal permeability is zonulin. In this study, we aimed to detect the value of zonulin as a diagnostic and prognostic marker in patients with different degrees of nonalcoholic fatty liver disease (steatosis, steatohepatitis, cirrhosis).This case–control study was conducted on 60 subjects in Gastroenterology and Bariatric Surgery Departments at Ain Shams University Hospitals who were divided into 3 groups: Group A: 20 patients underwent bariatric surgery and have mild NASH, Group B: 20 patients underwent bariatric surgery and have moderate-to-severe NASH, and Group C: 20 healthy controls, during a period 1 of year.ResultsThere was high statistically significant difference between the studied groups; as regard zonulin concentration, zonulin showed high diagnostic accuracy in diagnosis of NASH among hepatic patients with total accuracy of 81.7%, sensitivity of 72.5%, and specificity of 100.ConclusionSerum zonulin levels increase with steatosis severity in patients with NAFLD. This explains the high diagnostic accuracy of zonulin in diagnosis and prognosis of NASH among patients.

Post-contrast CT liver attenuation alone is superior to the liver-spleen difference for identifying moderate hepatic steatosis.

To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values. A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis. The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver-spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver-spleen difference of -40 HU and -10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate-severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001). Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less. Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection. The liver-spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver-spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone.

Association of systemic inflammatory indices with anthropometric measures, metabolic factors, and liver function in non-alcoholic fatty liver disease

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18–55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.

Partial lipodystrophy: Clinical presentation and treatment

Lipodystrophic syndromes are acquired or genetic rare diseases, characterized by a generalized or partial lack of adipose tissue leading to metabolic alterations linked to strong insulin resistance. They are probably underdiagnosed, especially for partial forms. They are characterized by a lack of adipose tissue or a lack of adipose development leading to metabolic disorders associated with often severe insulin resistance, hypertriglyceridemia and hepatic steatosis. In partial forms of lipodystrophy, these mechanisms are aggravated by excess visceral adipose tissue and/or subcutaneous adipose tissue in the upper part of the body. Diagnosis is based on clinical examination, pathological context and comorbidities, and on results of metabolic investigations and genetic analyses, which together determine management and genetic counseling. Early lifestyle and dietary measures focusing on regular physical activity, and balanced diet avoiding excess energy intake are crucial. They are accompanied by multidisciplinary follow-up adapted to each clinical form. When standard treatments have failed to control metabolic disorders, the orphan drug metreleptin, an analog of leptin, can be effective in certain forms of lipodystrophy syndromes.

Magnetic liver retraction in bariatric surgery: Is it possible?

One of the recent advances in bariatric surgery is the use of magnetic devices. This research paper describes magnetic liver retraction in morbidly obese patients during bariatric surgery. A descriptive, prospective and observational study was carried out, analyzing 100 patients in whom magnetic retraction was used. Mean and SD body mass index was 46.1 ± 5.09 kg/m2. The magnetic system was successfully used for liver retraction in 95% of cases; in only 5% of cases was its use not possible due to hepatomegaly and severe hepatic steatosis. According to the results, magnetic liver retraction can be safe and used in bariatric surgery, regardless of body mass index and with a low percentage of complications.

The association between serum fructosamine and random spot urine fructose levels with the severity of non-alcoholic fatty liver disease - an analytical cross-sectional study.

Non-alcoholic fatty liver disease (NAFLD) in South Africa and Africa at large is considered a hidden threat. Our local population is burdened with increased metabolic risk factors for NAFLD. Our setting requires a reasonable approach to screen for and aid the diagnosis of NAFLD. To investigate serum fructosamine and random spot urine fructose levels as biomarkers for the screening, diagnosis and monitoring of NAFLD. The primary objective of this study was to compare serum fructosamine and random spot urine fructose levels between groups with different levels of NAFLD severity as measured by ultrasound. A secondary objective was to determine the association, if any, between serum transaminases, the aspartate aminotransferase (AST) to platelet ratio index (APRI) score, serum fructosamine and urine fructose in different groups with steatosis. Using a cross-sectional study design, 65 patients with three different levels of NAFLD, as detected by imaging, were enrolled. The primary exposures measured were serum fructosamine with random spot urine fructose, and secondary exposures were the serum transaminases (AST and alanine aminotransferase (ALT)) and the APRI score. Patients identified at the departments of gastroenterology, general internal medicine and diagnostic radiology were invited to participate. There were 38, 17 and 10 patients with mild, moderate and severe steatosis, respectively. There was no significant difference between the groups regarding serum fructosamine, measured as median (interquartile range): mild 257 (241 - 286) μmol/L, moderate 239 (230 - 280) μmol/L and severe 260 (221 - 341) μmol/L, p=0.5; or random spot urine fructose: mild 0.86 (0.51 - 1.30) mmol/L, moderate 0.84 (0.51 - 2.62) mmol/L and severe 0.71 (0.58 - 1.09) mmol/L, p = 0.8. ALT (U/L) differed between groups: mild 19 (12 - 27), moderate 27 (22 - 33), severe 27 (21 - 56), p=0.03, but not AST (U/L) (p=0.7) nor APRI (p=0.9). Urine fructose and ALT were correlated in the moderate to severe steatosis group (R=0.490, p<0.05), but not in the mild steatosis group. Serum fructosamine was associated with age in the mild steatosis group but not the moderate-severe steatosis group (R=0.42, p<0.01). Serum fructosamine and random spot urine fructose did not vary with the severity of NAFLD, indicating that they would not be useful biomarkers in this condition.

Accelerometer-based sedentary time and physical activity with MASLD and liver cirrhosis in 2684 British adolescents

Evidence on the long-term relationship of sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous PA (MVPA) with liver steatosis, fibrosis, cirrhosis, and changes in liver enzymes in the paediatric population is limited. This study examined the associations of cumulative ST, LPA and MVPA from childhood with longitudinal changes in liver indices and enzymes. From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-points accelerometer-measured ST, LPA and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography and staged as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), the prevalence of liver steatosis at age 17 years was 2.6% and 20.5% at age 24 years. The cumulative 1-minute/day increase in ST from ages 11–24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002–1.005] p < 0.001) and severe liver steatosis (1.001 [1.001–1.002] p = 0.002) at age 24 years. Increased ST from childhood was directly associated with progressively increased ALT, AST and GGT from ages 17 to 24 years. Cumulative 1-min/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990–0.991] p < 0.001) and severe liver steatosis (0.999 [0.998–0.999] p < 0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-min/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994–0.998] p < 0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. In conclusion, increasing LPA, sustaining MVPA and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and liver cirrhosis by young adulthood.

Association between the arm circumference and non-alcoholic fatty liver disease in American children and adolescence: a population-based analysis.

The arm circumference (AC) has been used as an important tool to access the risk of non-alcoholic fatty liver disease (NAFLD) in adults. However, the association between AC and NAFLD in children and adolescence remains unclear. This study aims to explore the relationship between AC and NAFLD in American children and adolescence. 2017-2020 National Health and Nutrition Examination Survey (NHANES) was used to carry out the cross-sectional study. The association between AC and the risk of NAFLD, and liver steatosis was analyzed using weighted multivariable logistic regression and multivariate linear regression. Additionally, a two-part linear regression model was used to identify threshold effects in this study. Subgroup analysis, interaction tests and receiver operating characteristic (ROC) curve analysis were also carried out. A total of 1,559 children and adolescence aged 12-18 years old were included, and the prevalence of NAFLD was 27.3%. AC was positively correlated with the risk of NAFLD (OR = 1.25, 95% CI: 1.19, 1.32) and liver steatosis (β = 4.41, 95% CI: 3.72, 5.09). Subgroup analysis stratified by age and race showed a consistent positive correlation. A non-linear relationship and saturation effect between AC and NAFLD risk were identified, with an S shaped curve and an inflection point at 34.5 cm. Area under the ROC of AC to NAFLD was 0.812, with the sensitivity of 67.6%, the specificity of 83.8% and the cutoff value of 31.7 cm. Our study shows that AC is independently correlated with an increased risk of NAFLD and the severity of liver steatosis in American children and adolescence.

Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis.

Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Insights into the molecular mechanisms of malnutrition-associated steatohepatitis: A review.

Malnutrition is a public health epidemic mainly targeting poverty-stricken people, young ones, older people, pregnant women, and individuals with metabolic disorders. Severe malnutrition is linked with several metabolic defects, such as hepatic dysfunction, hypertension, cardiovascular disease, and osteoarthritis. The proper functioning of the liver plays a crucial role in ensuring the supply of nutrients to the body. Consequently, inadequate nutrition can lead to severe periportal hepatic steatosis due to compromised mitochondrial and peroxisome functions. Reduced protein intake disrupts essential metabolic processes like the TCA cycle, oxidative phosphorylation, and β-oxidation, ultimately affecting ATP production. Furthermore, this can trigger a cascade of events, including disturbances in amino acid metabolism, iron metabolism, and gut microbiota, which activate genes involved in de novo lipogenesis, leading to the accumulation of lipids in the liver. The condition, in prolonged cases, progresses to steatohepatitis and liver fibrosis. Limited therapeutic solutions are available; however, few dietary supplements and drugs have demonstrated positive effects on the growth and health of malnourished individuals. These supplements improve parameters such as inflammatory and oxidative status, reduce triglyceride accumulation, enhance insulin sensitivity, and downregulate gene expression in hepatic lipid metabolism. This review elucidates the various mechanisms involved in malnutrition-associated steatohepatitis and provides an overview of the available approaches for treating this condition.

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).