Severity Of Nonalcoholic Fatty Liver Disease Research Articles

Influence of nonalcoholic fatty liver disease severity on carotid adventitial vasa vasorum

IntroductionNonalcoholic fatty liver disease (NAFLD) affects a quarter of the world’s population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis.Material and methodsThis cross-sectional study aimed to explore the relationship between NAFLD severity, assessed via liver biopsy, and early atherosclerosis using adventitial vasa vasorum (VV) density. It included 44 patients with obesity (33 with steatosis, 11 with NASH) undergoing bariatric surgery.ResultsResults revealed no significant differences in adventitial VV density between steatosis and NASH groups, neither in the mean values [0.759 ± 0.104 vs. 0.780 ± 0.043, P=0.702] nor left-right sides. Similarly, carotid intima-media thickness (cIMT) did not vary between these groups. Additionally, no linear correlation existed between VV density and cIMT. Only gender showed an association with VV density.ConclusionThese findings suggest that NASH severity doesn’t independently drive early atherosclerosis or affects cIMT. Gender might play a role in early atherosclerotic disease in NAFLD, impacting VV density and cIMT. This highlights the need to consider other risk factors when evaluating cardiovascular risk in NAFLD patients.

Linking Non-alcoholic Fatty Liver Disease Severity With Metabolic Syndrome Features: An Integrative Study on Clinical and Radiological Fronts

Linking Non-alcoholic Fatty Liver Disease Severity With Metabolic Syndrome Features: An Integrative Study on Clinical and Radiological Fronts

A prospective observational cross-sectional study on the association of non-alcoholic fatty liver disease and insulin resistance in acute ischemic stroke in tertiary care hospital in Central India

Background Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance have individually been associated with increased cardiovascular risk, and their potential interplay in the context of Acute Ischemic Stroke remains a subject of investigation. This study aims to elucidate the association between NAFLD, insulin resistance, and Acute Ischemic Stroke, exploring risk factors, etiology, and potential implications for patient management. Methods This prospective observational cross-sectional study will be conducted at Acharya Vinoba Bhave Rural Hospital, enrolling patients aged 40-79 diagnosed with acute ischemic stroke between 2022 and 2025. Diagnostic confirmation will involve brain imaging, and abdominal ultrasonography will assess NAFLD severity. Biochemical parameters will be measured for insulin resistance evaluation, including blood glucose, glycosylated hemoglobin (HbA1c), and fasting insulin levels. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) will be calculated. Statistical analyses, including descriptive statistics and bivariate and multivariate analyses, will be applied to explore associations and potential risk factors. Expected Outcome Anticipated findings include insights into the prevalence and severity of NAFLD in Acute Ischemic Stroke patients, the association between insulin resistance and stroke incidence, and potential risk factors contributing to this association. The study provides a foundation for understanding the complex relationship between NAFLD, insulin resistance, and Acute Ischemic Stroke, offering valuable implications for risk stratification and patient management in clinical practice. Identifying modifiable risk factors may guide targeted interventions, contributing to improved outcomes in this patient population.

Anthropometry, Laboratory, and PNPLA3 Polymorphisms in a Novel Model for Early identification and Evaluation of Nonalcoholic Fatty Liver Disease.

BackgroundSome anthropometric, laboratory, and genetic variations, such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic variants, have been associated with nonalcoholic fatty liver disease (NAFLD). Liver biopsy is the most accurate NAFLD diagnostic method, but it is invasive; hence, noninvasive diagnostics are required for the early diagnosis and assessment of NAFLD. Patient and MethodsThis prospective case-control study included 107 NAFLD patients and 107 healthy controls. All individuals underwent anthropometric measurements, abdominal ultrasonography, laboratory tests, and evaluation for PNPLA3 polymorphisms. ResultsPatients with NAFLD had higher levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) than healthy individuals (p = 0.03, p < 0.0001). Additionally, patients with NAFLD had substantially lower albumin (P = 0.01) and leptin (P < 0.0001) levels than healthy individuals. BMI leptin and CRP levels were independent indicators of NAFLD severity (p = 0.05–0.004). GG is the most prevalent genotype in patients with moderate to severe NAFLD. A novel model based on four markers (leptin, CRP, BMI, and PNPLA3 polymorphism) was developed. The AUC values for distinguishing between the healthy subjects and those with varying degrees of NAFLD severity (mild, moderate, and severe) were 0.99, 0.99, and 1.0, respectively. ConclusionAnthropometric measurements, such as BMI and laboratory results, including liver enzymes, CRP, inflammatory markers, lipid parameters, and genetic markers, especially PNPLA3 polymorphisms, can provide an accurate, sensitive, and specific noninvasive approach for the early identification and assessment of NAFLD and can guide its management. This may minimize the need for liver biopsy to assess NAFLD. Further large-scale studies are needed to confirm these findings and verify the model in larger studies.

Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent along with the increasing trend of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. One hundred twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 groups according to body mass index (BMI). Ninety two were obese, and 19 and 10 were overweight and normal weight, respectively. The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (P=0.044). The TyG index and US-FLI did not differ significantly among the 3 BMI groups (P=0.186). Fourteen (11.6 %) of the 121 patients had US-FLI  6, in whom the BMI-SDS and TyG index were higher (P=0.017, P=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI < 6 (P=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI  6 was 8.91, with an area under the curve of 0.785. TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

Hepatokine ITIH3 protects against hepatic steatosis by downregulating mitochondrial bioenergetics and de novo lipogenesis

Recent studies demonstrate that liver secretory proteins, also known as hepatokines, regulate normal development, obesity, and simple steatosis to non-alcoholic steatohepatitis (NASH) progression. Using a panel of ∼100 diverse inbred strains of mice and a cohort of bariatric surgery patients, we found that one such hepatokine, inter-trypsin inhibitor heavy chain 3 (ITIH3), was progressively lower in severe non-alcoholic fatty liver disease (NAFLD) disease states highlighting an inverse relationship between Itih3/ITIH3 expression and NAFLD severity. Follow-up animal and cell culture models demonstrated that hepatic ITIH3 overexpression lowered liver triglyceride and lipid droplet accumulation, respectively. Conversely, ITIH3 knockdown in mice increased the liver triglyceride in two independent NAFLD models. Mechanistically, ITIH3 reduced mitochondrial respiration and this, in turn, reduced liver triglycerides, via downregulated de novo lipogenesis. This was accompanied by increased STAT1 signaling and Stat3 expression, both of which are known to protect against NAFLD/NASH. Our findings indicate hepatokine ITIH3 as a potential biomarker and/or treatment for NAFLD.

A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Non-alcoholic Fatty Liver Disease Among Iraqi Patients With Psoriasis: A Case-Control Study.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Several studies have shown that patients with psoriasis have a higher risk of developing NAFLD. Obesity, metabolic syndrome, and cytokine-mediated inflammation might be the link between psoriasis and NAFLD. This study aims to investigate the prevalence of NAFLD among psoriatic Iraqi patients and examine the relationship with disease severity using the Psoriasis Area and Severity Index (PASI) score and the correlation with different clinical and laboratory parameters. A case-control study on 130 psoriatic patients and 130 age-, sex-, and BMI-matched healthy controls was conducted at the Department of Dermatology in Basra Teaching Hospital from November 2022 to October 2023. All demographic and clinical data were collected using a pre-designed questionnaire, and NAFLD was diagnosed through a FibroScan examination performed on each participant. The severity of psoriasis was determined using the PASI score. Fasting glucose, liver enzymes, and lipid profile levels were investigated, and metabolic syndrome was identified. The prevalence of NAFLD was significantly higher in our psoriatic patients than in the control group (66.2% vs. 42.3%, OR=2.6, P<0.01). Psoriatic patients were found to have more severe NAFLD than the controls, as evidenced by their steatosis and fibrosis staging (P<0.01). In patients with psoriasis, NAFLD was associated with a higher prevalence of diabetes (17.4%) and metabolic syndrome (55.8%). Furthermore, psoriatic patients with NAFLD had significantly higher values of BMI, waist circumference, PASI score, as well as serum alanine transaminase (ALT), triglyceride, cholesterol, low-density lipoprotein (LDL), and fasting glucose levels.The study also found a significant positive correlation between the psoriasis severity based on PASI and the steatosis score. Metabolic syndrome, PASI, BMI, serum triglycerides, LDL, and age are the independent predictors of NAFLD. NAFLD is highly prevalent among psoriatic patients affecting more than half of them and closely associated with metabolic syndrome and severity of psoriasis. Routine screening for NAFLD may be necessary in psoriatic patients particularly when considering the use of hepatotoxic drug therapy.

Circulating Bone morphogenetic protein 9(BMP9) as a new biomarker for noninvasive stratification of nonalcoholic fatty liver disease and metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome (MetS). Bone morphogenetic protein 9 (BMP9) is an essential factor in glucose, lipid and energy metabolism. This study aims to investigate whether BMP9 can serve as a serological marker for the severity of NAFLD or MetS. Blood samples, clinical data and FibroTouch test were collected from consecutively recruited 263 individuals in Shanghai East hospital. All the participants were divided into three groups: the healthy controls, nonalcoholic fatty liver (NAFL) group and nonalcoholic steatohepatitis (NASH) at-risk group according to the results of FibroTouch test and liver function. Serum BMP9 levels were measured by enzyme-linked immunosorbent assay. Serum BMP9 levels were positively correlated with transaminase, triglyceride, fasting plasma glucose, glycated hemoglobin (HbA1c) and uric acid while it showed a downward trend as the increasing number of MetS components. Furthermore, it differentiated NASH at-risk (58.13 ± 2.82ng/L) from the other groups: healthy control (70.32 ± 3.70ng/L) and NAFL (64.34 ± 4.76ng/L) (p < 0.0001). Controlled attenuation parameter of liver fat and liver stiffness measurement were negatively correlated with BMP9 levels, while high-density lipoprotein levels were positively correlated. The risk of developing NAFLD increased along with elevated serum BMP9 and BMI, and a significantly higher risk was observed in men compared to women. BMP9 should be considered a protective factor for the onset and development of NAFLD, as well as a promising biomarker for the severity of the NAFLD and MetS.

Non-Hispanic Black persons with nonalcoholic fatty liver disease have lower rates of advanced fibrosis, cirrhosis, and liver-related events even after controlling for clinical risk factors and PNPLA3 genotype.

Nonalcoholic fatty liver disease (NAFLD) is less frequent in non-Hispanic persons (NHB) but there are knowledge gaps in our understanding of disease severity and outcomes of NAFLD in NHB. We compared liver histology and clinical outcomes of NAFLD in NHB and non-Hispanic White adults (NHW). We compared liver histology and outcomes of 109 NHB and 1910 NHW adults with biopsy proven NAFLD participating in the Nonalcoholic Steatohepatitis Clinical Research Network observational studies. The relationship between self-reported NHB race/ethnicity and advanced fibrosis was assessed via multivariable logistic regression after controlling for clinical co-variates and PNPLA3 genotype. NHB and NHW with NAFLD had similar NAFLD activity scores (NAS, 4.4 vs 4.3, p=0.87) and proportions with definite NASH (59% vs 58%, p=1.0), but NHB had significantly lower rates of advanced fibrosis (22% vs 34%, p=0.01) or cirrhosis (4.6% vs 12.1%, p=0.010). Compared to NHW, NHB had significantly lower frequency of advanced fibrosis (OR: 0.48, 95% CI:.27-0.86, p=0.01). In a comparison between 24 NHB and 655 NHW with advanced fibrosis, the NAS (5.6 vs 4.9, p=0.01) and lobular inflammation grade (2.2 vs 1.7, p<0.002) were significantly higher among NHB with advanced fibrosis. One NHB and 23 NHW died during follow-up (0.30 vs 0.28 per 100 person-year follow-up). Seven and zero liver-related deaths occurred in NHW and NHB with NAFLD respectively. The risk of advanced fibrosis in NHB with NAFLD is significantly lower, after controlling for clinical risk factors and PNPLA3 genotype. Although their risk for advanced fibrosis was low, NHB with NAFLD and advanced fibrosis had higher NAS and lobular inflammation, indicating a difference in their relationship between necroinflammation and fibrosis.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Relationship between serum β-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum β-hydroxybutyrate (β-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum β-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum β-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum β-HB correlated with liver mitochondrial β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum β-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum β-hydroxybutyrate (β-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating β-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum β-HB. Our work supports serum β-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Histopathological Association of Non-alcoholic Fatty Liver Disease With Coronary Artery Atherosclerosis Grade

Background: The association between the severity of coronary atherosclerosis and histopathologic findings in patients with non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Considering the gold standard method, this study evaluates the histopathologic association between the severity of NAFLD and the grades of coronary atherosclerosis. Methods: In this descriptive-analytical study, data from 205 cadavers who were referred to an Iranian (Tabriz) forensic medicine organization between 2015 and 2017 and underwent simultaneous liver and coronary artery biopsies were examined. Finally, 168 cases were entered based on the inclusion criteria. First, pathological slides of these cadavers were extracted from the forensic medicine archive and re-examined. Then, the selected cases’ blocks were extracted from the tissue block bank, and again, after preparing a new slide, they were stained with trichrome for accurate estimation of liver fibrosis. Results: The assessment of NAFLD histological status in the studied cases revealed that 75.6% of the cases were classified as severity I, 18.4% as severity II, and 6% as severity III. Most cases with coronary atherosclerosis were classified as American Heart Association staging (AHA), type V (19.6%), and normal (19.6%). There was no statistically significant relationship between the severity of simple steatosis, steatohepatitis, and NAFLD, with coronary atherosclerosis. In subjects with higher severity of coronary atherosclerosis, the liver fibrosis rate is also higher, but no statistically significant difference was observed. Conclusion: The present study revealed no significant histopathological association between NAFLD and coronary artery atherosclerosis grade.

Comparison of size of the liver between patients with non-alcoholic fatty liver disease and healthy controls.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease across all age groups. Limited studies have been conducted to consider the relationship between NAFLD and liver size. This study aimed to compare the size of the liver between NAFLD patients and healthy controls. This case-control study was conducted on NAFLD patients (n = 300), and healthy subjects (n = 300) referred to the Golestan Hospital of Ahvaz from April to August 2021. All individuals underwent ultrasonography examination, and liver size was measured in the midclavicular line. Fatty liver was divided into three grades, I (mild), II (moderate), and III (severe), according to the disease severity. Anthropometric parameters, including age, sex, weight, height, and body mass index (BMI), were recorded. Finally, the size of the liver and its relationship with NAFLD and anthropometric parameters was evaluated. Patients had significantly higher weight, and BMI mean values than controls (P < 0.001). In comparison to controls, NAFLD patients had considerably larger livers on average. (149.05 ± 12.60 mm vs. 134.51 ± 12.09; P < 0.001). There was a significant tendency for larger liver size in normal to severe fatty liver patients (P < 0.001). In patients with mild, moderate, and severe NAFLD, the mean liver size was 144.34 ± 11.35, 154.21 ± 10.84, and 158.63 ± 13.45 mm, respectively. The mean liver size in both groups was significantly higher in males than females (P < 0.05). Age (P = 0.037), sex (P < 0.001), height (P < 0.001), BMI (P = 0.008), and steatosis (P < 0.001) were independent variables for predicting the liver size. The liver size of persons with fatty liver was substantially more considerable than healthy people. The size of the liver was substantially linked with sex, age, BMI, fatty liver, and hepatic steatosis grade. A straightforward way to predict fatty liver is to use ultrasonography to determine the size of the liver.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease.

Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Comparison of Serum C-Reactive Protein (CRP) Level Between Non-Alcoholic Fatty Liver Disease (NAFLD) Cases and Healthy Adults: A Cross-sectional Analytical Study.

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis and cirrhosis. Though accurate diagnosis of simple fatty liver (SFL) and non-alcoholic steatohepatitis (NASH) can be made by liver biopsy, it is not feasible to be done in all NAFLD patients. Relationship of C-reactive protein (CRP) with NAFLD was well documented in many populations, but comprehensive data is lacking in Bangladeshi people. Method: This case-control study was conducted at the Medicine, Gastroenterology and Hepatology departments in Dhaka Medical College Hospital from March to August 2018 involving 30 patients with NAFLD as case and apparently healthy 30 individuals as control. Abdominal ultrasound to detect fatty liver and serum CRP level estimation by nephelometry were performed for each subject to compare between two groups. Result: Majority of the NAFLD cases and healthy controls were female (70% and 60% respectively). Mean age was 47.53±9.69 year in NAFLD group and 46.03±8.44 year in healthy controls. NAFLD cases had significantly higher mean serum CRP concentration (6.27±1.80) mg/dl than that of healthy controls (3.94±2.16) mg/dl (p&lt;0.001). Overweight/obesity and dyslipidaemia were found as significant risk factors for NAFLD compared to the healthy control group (p&lt;0.05). Conclusion: NAFLD cases had significantly higher CRP than the control group. But, to find out the association of increasing CRP level with the severity of NAFLD and to establish it as a diagnostic tool, further extensive studies are recommended. J MEDICINE 2024; 25: 5-10

Prunus mume extract and choline treatment in patients with non-alcoholic fatty liver disease estimated by b-mode ultrasonography and hepatorenal index.

The aim of this study was to find the difference between the liver function test (LFT) and hepatorenal index (HRI), before and after the administration of Prunus mume (PM) and choline i.e., to find the predictors of the non-alcoholic fatty liver disease (NAFLD) severity according its HRI, during the three-month follow-up period. LFT, glucose, and lipid tests were determined in 168 NAFLD patients, at baseline and after three-month drug treatment. HRI was calculated by Image J software analyzing the ultrasound images, and according its value, 3 groups of NAFLD were formed. The HRI at baseline (1.3598±0.1744) and after 3 months therapy (1.3061±0.1923) differs significantly (p<0.0001). Plasma glucose (FPG) (p<0.0001), glycated hemoglobin (HbA1c) (P=0.002), alanine aminotransferase (ALT) (p<0.0001), aspartate aminotransferase (AST) (P=0.0006), gamma-glutamil transferase (γ-GT) (P=0.0053), high density lipoprotein cholesterol (HDL-Ch) (p<0.0001) and triglycerides (P=0.041) differ significantly, too. HRI is positively correlated with: HbA1c (P=0.035), ALT (P=0.002), AST (P=0.003), γ-GT (P=0.043), and triglycerides (P=0.002) and inversely correlated with HDL-Ch (P=0.011). In multiple regression results (standard coefficient and p-value), the independent predictors for HRI in NAFLD patients were: HbA1c (0.1443, 0.0004), ALT (0.001142, 0.0081), triglycerides (0.0431, 0.0235) and γ-GT (0.001376, 0.0329). Three-month administration of PM and choline have beneficial effects on the regulation of glucose and lipid metabolism (HDL-Ch), and on LFT. This plant extract significantly reduces the levels of FPG, HbA1c, ALT, AST, γ-GT, triglycerides and increases HDL-Ch. The triglycerides, ALT, γ-GT and HbA1c are positive independent predictors for the severity of NAFLD.

Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD

Background and aimThe excessive accumulation of lipid droplets (LDs) is a defining characteristic of nonalcoholic fatty liver disease (NAFLD). The interaction between LDs and mitochondria is functionally important for lipid metabolism homeostasis. Exercise improves NAFLD, but it is not known if it has an effect on hepatic LD-mitochondria interactions. Here, we investigated the influence of exercise on LD-mitochondria interactions and its significance in the context of NAFLD. Approach and resultsMice were fed high-fat diet (HFD) or HFD-0.1 % methionine and choline-deficient diet (MCD) to emulate simple hepatic steatosis or non-alcoholic steatohepatitis, respectively. In both models, aerobic exercise decreased the size of LDs bound to mitochondria and the number of LD-mitochondria contacts. Analysis showed that the effects of exercise on HOMA-IR and liver triglyceride levels were independent of changes in body weight, and a positive correlation was observed between the number of LD-mitochondria contacts and NAFLD severity and with the lipid droplet size bound to mitochondria. Cellular fractionation studies revealed that ATP-coupled respiration and fatty acid oxidation (FAO) were greater in hepatic peridroplet mitochondria (PDM) from HFD-fed exercised mice than from equivalent sedentary mice. Finally, exercise increased FAO and mitofusin-2 abundance exclusively in PDM through a mechanism involving the curvature of mitochondrial membranes and the abundance of saturated lipids. Accordingly, hepatic mitofusin-2 ablation prevented exercise-induced FAO in PDM. ConclusionsThis study demonstrates that aerobic exercise has beneficial effects in murine NAFLD models by lessening the interactions between hepatic LDs and mitochondria, and by decreasing LD size, correlating with a reduced severity of NAFLD. Additionally, aerobic exercise increases FAO in PDM and this process is reliant on Mfn-2 enrichment, which modifies LD-mitochondria communication.