Severe Steatosis Research Articles

LIVER FIBROSIS AND STEATOSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A TRANSIENT ELASTOGRAPHY STUDY

Background :The prevalence of non-alcoholic fatty liver disease is notably high among patients with type 2 diabetes mellitus (T2DM). The objective of this study was to assess the potential utility of transient elastography (TE), a technique capable of measuring both fibrosis and liver fat content simultaneously, as a screening tool for hepatic involvement in patients with T2DM. Material and methods : Its a retrospective study spanned from January 2019 to January 2024 and included all patients diagnosed with T2DM who underwent TE. LSM values were determined using a Fibroscan 502 touch (Echosens SA, Paris, France) with the original M or XL probe selected based on the patients body weight or subcutaneous adipose tissue thickness, as per the manufacturers guidelines. TE scans were considered reliable when a minimum of 10 successful acquisitions were obtained, and the interquartile range-to-median ratio of the 10 acquisitions was ≤0.3. Results : A total of 124 patients with T2DM who underwent TE examination were included. 46 males and 78 females. The mean BMI of the patients was 33.2±6.6 kg/m2. The mean LSM was 7.1±3.4 kPa. LSM values exhibited significant correlations with BMI (p<0.001) and AST (p<0.001). The mean CAP value was 317±54 dB/m. Univariate correlation analyses demonstrated significant associations between CAP values and BMI (p<0.001). We found higher ALT levels (p<0.05) in patients with F3/F4 fibrosis. Both patients with mild and severe steatosis had higher ALT levels than those without (both p<0.05). However, ALT values did not differ significantly according to steatosis severity (p=0.69). Conclusion : Our results contribute to the existing body of evidence across various studies, approving the clinical utility of LSM and CAP for concurrent screening of liver fibrosis and steatosis in patients with T2DM.

От неалкогольной к метаболически ассоциированной жировой болезни печени. Стеатометрия и кардиометаболические факторы как предикторы развития стеатогепатита

Non-alcoholic metabolic dysfunction-associated fatty liver disease is the most common liver sickness linked with the high risk of hepatic and extrahepatic complications. The article provides an overview of changes in the nomenclature of this disease, analysis of risk factors for its development and the results of own research. The aim of the study was to estimate the clinical significance of steatometry (CAP function) by Fibroscan and cardiometabolic factors in assessing the risk of steatohepatitis development. Material and methods. Patients with hepatic steatosis accompanied by metabolic disorders were examined. Steatometry as well as routine physical and laboratory examination, including biochemical blood tests and abdominal ultrasound were provided. Statistical analysis included χ2 test, Spearman's rank correlation test, Student's t-test, Mann–Whitney test, multiple linear regression analysis. Results. 74 patients were included. Main characteristics of the cohort: 62.2% male, mean age – 48.8 years, cases of steatohepatitis – 41.9%. It was revealed that the number of metabolic factors in an individual patient correlated with the presence of steatohepatitis (χ2 = 3.29; p < 0.05) and the severity of steatosis by steatometry (rs = 0.37; p < 0.05). Individual clinical and laboratory parameters influenced the severity of steatosis with varying degrees. The most significant parameters were: abdominal circumference, concentration of HDL, insulin, activity of ALT, GGTP, and the presence of arterial hypertension. Using these indicators, a formula for assessing the risk of severe liver steatosis was created. Conclusion. Steatometry is to be considered as an important diagnostic method for the prognosis assessment in patients who have risk factors for the development and progression of non-alcoholic metabolic dysfunction-associated fatty liver disease. Severe steatosis is a predictor of steatohepatitis. The number of metabolic factors present in an individual patient is important in assessing the risk of severe liver steatosis and steatohepatitis.

Systemic Oxidative Balance Reflects the Liver Disease Progression Status for Primary Biliary Cholangitis (Pbc): The Narcissus Fountain.

Biological antioxidant potential (BAP) and Reactive Oxygen Metabolites (dROMs) are two tests complementarily assessing systemic oxidative statuses (SOSs) that are never applied in chronic liver disorders (CLDs). We enrolled 41 ursodeoxycholic acid (UDCA)-naïve Primary Biliary Cholangitis (PBC) patients [age: 58.61 ± 11.26 years; females (F): 39], 40 patients with metabolic-dysfunction-associated steatotic livers (age: 54.30 ± 11.21; F: 20), 52 patients with HBV (age: 52.40 ± 8.22; F: 34), 50 patients with (age: 56.44 ± 7.79, F: 29), and 10 controls (age: 52.50 ± 9.64; F: 7). Liver fibrosis and the steatosis severity were determined using transient elastography, and the SOS was balanced using d-ROMs and the BAP test. The gene expressions of superoxide dismutase (SOD1; SOD2) and glutathione peroxidase (GPx1) were evaluated using real-time PCR in advanced fibrosis (AF: F3F4) in patients with PBC. In contrast to other CLDs, in PBC the dROMs and BAP levels were, respectively, directly and inversely correlated with hepatic fibrosis (dROMs, R: 0.883; BAP, R: -0.882) and steatosis (dROMs, R: 0.954; BAP, R: -0931) severity (p < 0.0001 all). Patients with PBC also revealed a progressively increasing trend of d-ROMs (F0-F2 vs. F3: p = 0.0008; F3 vs. F4: p = 0.04) and reduction in BAP levels (F0-F2 vs. F3: p = 0.0007; F3 vs. F4 p = 0.04) according to the worsening of liver fibrosis. In AF-PBC, the SOD1, SOD2, and GPx1 expressions were significantly downregulated in patients presenting SOS imbalance (SOD1, p = 0.02; SOD2, p = 0.03; GPx1, p = 0.02). SOS disequilibrium represents a leitmotiv in patients with PBC, perfectly reflecting their liver disease progression status.

Peripheral amyloid-β clearance mediates cognitive impairment in non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a prevalent risk factor for cognitive impairment. Cerebral amyloid-β (Aβ) accumulation, as an important pathology of cognitive impairment, can be caused by impaired Aβ clearance in the periphery. The liver is the primary organ for peripheral Aβ clearance, but the role of peripheral Aβ clearance in NAFLD-induced cognitive impairment remains unclear. MethodsWe examined correlations between NAFLD severity, Aβ accumulation, and cognitive performance in female Sprague-Dawley rats. The impact of NAFLD on hepatic Aβ clearance and the involvement of low-density lipoprotein receptor-related protein 1 (LRP-1) were assessed in rat livers and cultured hepatocytes. Additionally, a case-control study, including 549 NAFLD cases and 549 controls (782 males, 316 females), investigated the interaction between NAFLD and LRP-1 rs1799986 polymorphism on plasma Aβ levels. FindingsThe severity of hepatic steatosis and dysfunction closely correlated with plasma and cerebral Aβ accumulations and cognitive deficits in rats. The rats with NAFLD manifested diminished levels of LRP-1 and Aβ in liver tissue, with these reductions inversely proportional to plasma and cerebral Aβ concentrations and cognitive performance. In vitro, exposure of HepG2 cells to palmitic acid inhibited LRP-1 expression and Aβ uptake, which was subsequently reversed by a peroxisome proliferator-activated receptor α (PPARα) agonist. The case-control study revealed NAFLD to be associated with an increment of 8.24% and 10.51% in plasma Aβ40 and Aβ42 levels, respectively (both P <0.0001). Moreover, the positive associations between NAFLD and plasma Aβ40 and Aβ42 levels were modified by the LRP-1 rs1799986 polymorphism (P for interaction = 0.0017 and 0.0015, respectively). InterpretationLRP-1 mediates the adverse effect of NAFLD on peripheral Aβ clearance, thereby contributing to cerebral Aβ accumulation and cognitive impairment in NAFLD. FundingMajor International (Regional) Joint Research Project, National Key Research and Development Program of China, National Natural Science Foundation of China, and the Angel Nutrition Research Fund.

Association of Histopathological and Biochemical Aspects of NAFLD With the Severity of Liver Fibrosis in Individuals With Obesity: Cross-sectional Study.

Given the importance of fibrosis in the progression of non-alcoholic fatty liver disease (NAFLD), identifying biochemical and histopathological aspects associated with its severity is important to determine the course of disease in high-risk populations. The study aims to investigate correlations between biochemical and histopathological variables associated with the occurrence and severity of NAFLD-related liver fibrosis in individuals with obesity. This is a cross-sectional study which enrolled 171 individuals who underwent bariatric surgery at a tertiary university hospital. Clinical, laboratory, and histopathological hepatic characteristics were analyzed. Univariate and multivariate analyses were carried out to identify factors associated with the outcomes studied (severity of fibrosis staging) through simple and multiple regression models. Female were 87.7%, and the mean age was 38.4 ± 9.3years. The most common histopathological abnormalities were macrovesicular steatosis (74.9%) and hepatocellular ballooning (40.4%). In the histopathological univariate analysis, liver fibrosis significantly correlated with severities of microvesicular steatosis (p = 0.003), lobular inflammation (p = 0.001), and NAS (p < 0.001). In the multivariate analysis, the degrees of microvesicular steatosis (p < 0.001) and NAS (p < 0.001) independently correlated with fibrosis severity. In the univariate biochemical analysis, fibrosis severity significantly correlated with levels of hemoglobin A1c (p = 0.004) and glucose (p = 0.01). In the multivariate analysis, glucose levels independently correlated with liver fibrosis degree (p = 0.007). Significant and independent associations were observed between the intensities of microvesicular steatosis, NAS, and glucose levels and the severity degree of liver fibrosis in individuals with obesity.

Dynamics of the functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy

The aim. To evaluate the dynamics of metabolic status, functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy (MGT). Materials and methods. 40 menopausal women were examined, of which 25 patients with metabolic syndrome with an average age of 51.2 ± 1.2 years and 15 practically healthy women of 50.2 ± 1.9 years. anamnesis was collected, the presence of vasomotor symptoms was assessed, anthropometric data was measured with the calculation of body mass index, laboratory examination, including determination of blood levels of sex hormones, functional liver tests, metabolic parameters and markers of endothelial dysfunction- endothelin-1, vascular endothelial growth factor, the number of desquamated endotheliocytes and the activity of Willebrand factor, instrumental examination, including ultrasound examination of the liver and assessment of the vascular response to local heating on the Microtest device (Russia), as well as calculation of the Hepatic steatosis index (HSI). Results. In patients with metabolic syndrome in menopause, vasomotor symptoms, complaints of dysuria, dyspeptic phenomena were observed, an increase in blood pressure was recorded in 60%, an increase in Kurlov’s ordinates in 24%, 36% were overweight, 64% were obese 1-2 degrees. According to ultrasound, liver steatosis was verified in 76% of patients, the HSI index &gt;36.0 was in all women with MS. Against the background of estrogen deficiency, the course of menopause in women was accompanied by insulin resistance, dyslipidemia, increased alkaline phosphatase levels in 28% of individuals and endothelial dysfunction with impaired physiological response to local heating, increased vascular tone, increased thrombogenic potential of the vascular wall and activation of angiogenesis mechanisms. Conclusion: MGT with Femoston ® 1 in continuous mode in women with metabolic syndrome reduces the severity of menopausal syndrome, insulin resistance and liver steatosis, improves anthropometric parameters and functional characteristics of the liver and endothelium, which reduces the risk of cardiovascular events in this risk group.

O91: The Negative Impact of Transplant Liver Steatosis is Significantly Exaggerated in Donation Following Circulatory Death: A National Cohort Study

Abstract Introduction The demand for liver transplantation is rising, as is the prevalence of steatotic liver disease. Steatotic grafts have inferior outcomes post-transplantation, perhaps related to increased sensitivity to ischaemia-reperfusion injury. We aimed to formally evaluate whether the impact of steatosis differs in grafts donated following brainstem (DBD) versus circulatory death (DCD). Methods The NHS registry on adult liver transplantation was reviewed retrospectively (2006-2019). We used multiple-imputation for missing data, and adjusted regression models with interaction terms to compare the impact of donor graft steatosis (visually-assessed) on transplant outcome in DCD versus DBD. Results 9217 adult recipients of deceased donor grafts were included (DBD=7349; DCD=1868). Multivariable cox regression revealed that the negative effects of moderate or severe steatosis on graft survival were significantly different in DCD and DBD livers (interaction P=0.011 and P=0.043). The largest impact was in DCD livers (aHR=1.851, 1.296-2.645, P=0.001 for moderate and aHR=5.426, 1.723-17.090, P=0.004 for severe steatosis). In contrast, steatotic livers did not suffer inferior longer-term graft survival in the DBD cohort, despite inferior early outcomes. Conclusion The impact of steatosis on transplant outcome differs significantly based on donor type, with a much larger negative impact in DCD, proving that steatotic livers are specifically sensitive to the DCD process. This highlights a high-risk group which should be the target of novel therapeutics to allow this growing sector of the donor pool to be safely utilised. In contrast, moderate-severe steatosis does not impact longer term outcome in DBDs, and such grafts can be transplanted with excellent outcome.

Fatigue, depression, and sleep disorders are more prevalent in patients with metabolic-associated fatty liver diseases.

To determine the prevalence and risk factors for depression, sleep disturbances, and exhaustion in MAFLD patients. Two hundred twenty-four consecutive patients with MAFLD attending the outpatient clinic from April to October 2023; were subjected to clinical evaluation, laboratory testing including non-invasive laboratory markers, fibroscan (measuring steatosis and fibrosis), and different quantitative and qualitative fatigue scores. A control group including 342 patients without MAFLD was taken. The prevalence of fatigue, depression, and sleeping disorders in the MAFLD group was 67.8%, 75%, 62.5% vs 21%, 16.4%, and 19.5% in the control group respectively ( P = <0.001, P = <0.001 and P = <0.001). MAFLD with fatigue was significantly associated with the presence and severity of steatosis and fibrosis by fibroscan ( P = <0.0001). By univariate and multivariate analysis: age, BMI, waist circumference, T2DM, hypertension, steatosis, fibrosis, and Fib-4 were considered risk factors for fatigue in the MAFLD group. The age, high social level, diabetes, hypertension, steatosis, fibrosis, and fib-4 were considered, by univariate and multivariate analysis, independent risk factors for depression in the MAFLD group. age, BMI, waist circumference, diabetes, hypertension, steatosis, fibrosis, and fib-4 were independent risk factors for sleep disorders in MAFLD. Fatigue, sleeping disorders, and depression are more prevalent in MAFLD patients than in the general population. The lower health utility scores in patients with MAFLD are associated with more advanced stages of the disease.

Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease.

The adverse effects of long-term use of proton pump inhibitors (PPIs) have led to growing concern. The association between PPIs use and the risks of nonalcoholic fatty liver disease (NAFLD) remains controversial. The aim of this study was to investigate the association between PPIs use and the risks of NAFLD among the general adult population in the United States. We performed a cross-sectional study by extracting data from the National Health and Nutrition Examination Survey of 2017 to 2018. The association between PPIs use and NAFLD risks was analyzed by weighted multivariate logistic regression. Among the 4238 participants included in this study, 2167 were diagnosed with NAFLD. In the multivariate logistic regression model, PPIs use was associated with increased risks of NAFLD [odds ratio (OR): 1.318, 95% CI: 1.044-1.663; P=0.020]. This association was nonsignificant in participants taking PPIs for ˂5 years (OR: 0.846, 95% CI: 0.579-1.238; P=0.390), whereas it remained significant in participants taking PPIs for more than 5 years (OR: 2.016, 95% CI: 1.366-2.975; P=0.031). Further analysis showed that the use of PPIs was positively associated with risks of severe hepatic steatosis (OR: 1.451, 95% CI: 1.034-2.036; P=0.031) but not with mild-to-moderate steatosis (OR: 1.242, 95% CI: 0.886-1.741; P=0.208). This study indicated that taking PPIs was associated with increased risks of NAFLD, especially severe hepatic steatosis. Awareness should be raised regarding the potential risks of NAFLD when prescribing PPIs.

Barriers to Exercise in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Patient Survey.

Although adequate physical activity is an essential component of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD), the majority of people with MASLD do not engage in regular exercise and lead sedentary lifestyles. We aimed to identify perceived barriers to exercise and to examine awareness about the role of exercise in the treatment of MASLD. Individuals aged 18 years and above were recruited from a hepatology outpatient clinic. MASLD severity was assessed using controlled attenuation parameter (CAP) and transient elastography (TE) determined liver stiffness measurement (LSM) for the severity of hepatic steatosis and fibrosis, respectively. An online questionnaire was administered to record self-reported exercise patterns, barriers to exercise, and knowledge regarding effectiveness of different types of exercise for MASLD. Eighty-one participants (57% female) with a mean age of 55.3 ± 13.4 years and a mean body mass index (BMI) of 33.8 ± 6.4 answered the questionnaire. The mean CAP score was 335.7 ± 47.8 dB/m, and the median LSM was 12.45 kPa. While most patients (83%) considered MASLD to be a serious health concern, 73% did not achieve the recommended exercise levels of ≥ 150 min of moderate-intensity physical activity per week, and 54% were unsure about the role of exercise in the treatment of MASLD. Commonly reported barriers to exercise included physical and mental health issues (57%), lack of time (43%), lack of enjoyment in exercising (31%), fatigue caused by exercise (24%), and others (25%). Most participants with MASLD were unaware of the role of exercise as a potential treatment option and were not achieving recommended exercise levels. Inadequate time, physical and mental health problems, lack of enjoyment in exercise, and fatigue were major barriers.

Generalization of deep learning models for hepatic steatosis grading using B-mode ultrasound images

Grayscale ultrasound remains a key modality for screening of hepatic steatosis due to its non-invasiveness and availability. While neural networks have shown promise in this field, their main drawback lies in their inability to generalize to diverse real-world settings. Variations in equipment, acquisition parameters, or population significantly affect model performance. Test-time adaptation, an unsupervised domain adaptation technique, overcomes these limitations by adjusting trained models during inference. Our retrospective study used two datasets collected in separate populations, with different scanners and protocols. We propose an adaptation method, using test-time batch normalization to selectively adjust BatchNorm layers based on test data for predicting steatosis grades. Comparing the non-adapted and adapted models, the mean absolute error (± standard deviation) in grading four severities of steatosis decreased from 0.92 ± 0.21 to 0.64 ± 0.22 . Specifically, for detection of steatosis the area under the curve increased from 0.76 ± 0.05 to 0.95 ± 0.02 when using the adapted model. Adapted models show promising results in improving performance compared to base models when testing data differ significantly from training data. Results suggest that the proposed method effectively addresses domain shift in diagnosing fatty liver using ultrasound images, reducing risks associated with deploying trained models.

Вплив елімінаційної дієти на функціональний стан шлунково-кишкового тракту та печінки в жінок фертильного віку із симптомним аденоміозом

The existence of food intolerances disrupts the work of the gastrointestinal tract and the liver, the symptoms of which are largely similar to those of adenomyosis. Purpose - to investigate the effect of the elimination diet on indicators of the functional state of the gastrointestinal tract and liver of women having symptomatic adenomyosis. Materials and methods. 120 women with symptomatic adenomyosis were divided into 4 groups: the Group I - 30 women who were treated with dienogest; the Groups ІІ, ІІІ and IV - 30 women each, who were prescribed an elimination diet taking into account the identified type of food intolerance. A comprehensive clinical examination, coprological examination, and ultrasound steatometry of the liver were performed. Statistical data was processed by the SPSS 21 program. Results. Compared with women of the Group I, patients of the Groups II, III, and IV showed a decrease in the pain symptoms of adenomyosis, the frequency of complaints from the digestive tract, amylorrhea, steatorrhea in feces, and markers of the inflammatory process in the intestine, as well as the frequency and severity of liver steatosis. Conclusions. The elimination diet, taking into account the identified type of food intolerance, has a positive effect on well-being, the functional state of the gastrointestinal tract and reduces the symptoms of the disease of childbearing age women with adenomyosis. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Breaking boundaries: Unraveling metabolic dysfunction-associated steatotic liver disease in children of India and Canada

Background: Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease in children. Its prevalence is rising globally, yet it is uncertain if its onset and severity vary between countries. We aimed to compare pediatric NAFLD in two Canadian and Indian tertiary care centers. Methods: This study was conducted as a retrospective cohort study and patient related details were retrieved from the electronic records and reviewed. Results: The study analyzed a total of 184 children with NAFLD/MASLD (94 from the Indian site and 89 from the Canadian site) with concordance between NAFLD and MASLD definitions. The Indian children had a higher proportion of symptomatic presentations and family history of metabolic disorders ( p = 0.0001) while the Canadian children had higher median weight, BMI, blood pressure, and waist circumference ( p &lt; 0.05). Indian children had higher hepatic transaminases and low density lipoprotein levels, while the Canadian site had higher serum insulin, blood glucose, homeostasis model assessment of insulin resistance, high density lipoprotein cholesterol levels, liver stiffness, and controlled attenuation parameter values ( p &lt; 0.05). Majority (78%) of the Canadian children who underwent liver biopsy had significant fibrosis (&gt;stage 2). In the overall cohort, waist circumference could be identified as an independent risk factor, irrespective of country of origin, predicting hepatic fibrosis. Conclusions: The study found significant differences between cohorts. Canadian children showed higher obesity grades and greater hepatic steatosis and fibrosis severity. To comprehend the underlying causes, future studies are imperative.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Comparative study of ultrasound attenuation analysis and controlled attenuation parameter in the diagnosis and grading of liver steatosis in non-alcoholic fatty liver disease patients

PurposeTo assess the diagnostic performance of Ultrasound Attenuation Analysis (USAT) in the diagnosis and grading of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) using Controlled Attenuation Parameters (CAP) as a reference.Materials and methodsFrom February 13, 2023, to September 26, 2023, participants underwent CAP and USAT examinations on the same day. We used manufacturer-recommended CAP thresholds to categorize the stages of hepatic steatosis: stage 1 (mild) − 240 dB/m, stage 2 (moderate) − 265 dB/m, stage 3 (severe) − 295 dB/m. Receiver Operating Characteristic curves were employed to evaluate the diagnostic accuracy of USAT and determine the thresholds for different levels of hepatic steatosis.ResultsUsing CAP as the reference, we observed that the average USAT value increased with the severity of hepatic steatosis, and the differences in USAT values among the different hepatic steatosis groups were statistically significant (p < 0.05). There was a strong positive correlation between USAT and CAP (r = 0.674, p < 0.0001). When using CAP as the reference, the optimal cut-off values for diagnosing and predicting different levels of hepatic steatosis with USAT were as follows: the cut-off value for excluding the presence of hepatic steatosis was 0.54 dB/cm/MHz (AUC 0.96); for mild hepatic steatosis, it was 0.59 dB/cm/MHz (AUC 0.86); for moderate hepatic steatosis, it was 0.73 dB/cm/MHz (AUC 0.81); and for severe hepatic steatosis, it was 0.87 dB/cm/MHz (AUC 0.87).ConclusionUSAT exhibits strong diagnostic performance for hepatic steatosis and shows a high correlation with CAP values.

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

Characteristics, toxicology and major organ pathology of deaths due to acute alcohol toxicity in Australia, 2011-2022.

Acute alcohol toxicity is a significant component of alcohol-related mortality. The study aimed to: (i) determine the circumstances of death and characteristics of fatal alcohol toxicity cases, 2011-2022; (ii) determine their toxicological profile and major autopsy findings; and (iii) determine trends in population mortality rates. Retrospective study of acute alcohol toxicity deaths in Australia, 2011-2022, retrieved from the National Coronial Information System. A total of 891 cases were identified, with a mean age of 49.2 years, 71.0% being male. Alcohol use problems were noted in 71.3%. In 57.5% death was attributed solely to acute alcohol toxicity, and combined acute alcohol toxicity/disease in 42.5%. There was evidence of sudden collapse in 24.9% of cases. The mean BAC was 0.331 g/100 mL (range 0.107-0.936), and spirits were the most commonly reported beverages (35.8%). Cases of combined toxicity/disease had significantly lower BACs than those attributed solely to alcohol toxicity (0.296 vs. 0.358 g/100 mL). Cardiomegaly was diagnosed in 32.5%, and severe coronary artery disease in 22.1%. Aspiration of vomitus was noted in 18.0%, and chronic obstructive pulmonary disease in 19.6%. Severe liver steatosis was present in 33.4% and 13.6% had cirrhosis. There was an average annual percentage increase in deaths of 7.90. The 'typical' case was a long-standing, heavy spirits drinker. BACs showed enormous variation and no arbitrary concentration may be deemed lethal. Clinically significant disease was associated with death at a lower BAC and people with such disease may be at increased risk of alcohol poisoning.

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity

BackgroundNonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PurposeThis study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. MethodsA NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. ResultsIn MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1β, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFβ, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. ConclusionOur study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.

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.

Diabetes Accelerates Steatohepatitis in Mice: Liver Pathology and Single-Cell Gene Expression Signatures

Glucose lowering independently reduces liver fibrosis in human NAFLD. We investigated the impact of diabetes on steatohepatitis and established a novel mouse model for diabetic steatohepatitis.Male C57BL/6J mice were fed a 60% high-fat diet (HFD) and injected with carbon tetrachloride (CCl4) and streptozotocin (STZ) to induce diabetes. The HFD+CCl4+STZ group displayed more severe liver steatosis, hepatocyte ballooning, and regenerative nodules compared to other groups. Diabetes upregulated inflammatory cytokine-associated genes and elevated the M1/M2 macrophage ratios in the liver. Single-cell RNA sequencing (scRNAseq) analysis of non-parenchymal cells in the liver showed that diabetes reduced the Kupffer cells and increased bone marrow-derived recruited inflammatory macrophages, such as Ly6Chi-RM. Diabetes globally reduced liver sinusoidal endothelial cells (LSECs). Furthermore, the upregulation of genes related to the receptor for advanced glycation end products (RAGE)/toll-like receptor 4 (TLR4) was observed in Ly6Chi-RM and LSECs under diabetes, suggesting a possible role of the RAGE/TLR4 signaling in the interaction between inflammatory macrophages and LSECs.The study established a novel diabetic steatohepatitis model using a combination of HFD, CCl4, and STZ. Diabetes exacerbates steatosis, hepatocyte ballooning, fibrosis, regenerative nodule formation, and the macrophage M1/M2 ratios triggered by HFD and CCl4. scRNAseq analysis indicates that diabetes activates inflammatory macrophages and impairs LSECs through the RAGE/TLR4 signaling pathway. These findings open avenues for discovering novel therapeutic targets for diabetic steatohepatitis.