Moderate Liver Research Articles

Even moderate liver fat accumulation below conventional fatty liver cutoffs is linked to multiple metabolomic alterations and gestational dysglycemia in Asian women of reproductive age

BackgroundIt is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia.MethodsLiver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation.ResultsThe optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat < 2.07%), Moderate (2.07% ≤ liver fat < 5.56%), and High (liver fat ≥ 5.56%) groups. Individual MetS traits showed worsening trends, going from Low to Moderate to High groups. Multiple plasma metabolomic alterations, previously linked to incident type 2 diabetes (T2D), were already evident in the Moderate group (adjusted for ethnicity, age, parity, educational attainment, and BMI). Both a cross-sectional multi-metabolite score for incident T2D and mid-gestational glucose area under the curve showed increasing trends, going from Low to Moderate to High groups (p < 0.001 for both). Gestational diabetes incidence was 2-fold (p = 0.23) and 7-fold (p < 0.001) higher in the Moderate and High groups relative to the Low group.ConclusionsIn Asian women of reproductive age, moderate liver fat accumulation below the conventional fatty liver cutoff was not metabolically benign and was linked to gestational dysglycemia. The newly derived cutoff can aid in screening individuals before adverse metabolic phenotypes have consolidated, which provides a longer window for preventive strategies.

Analysis of the clinical characteristics of HBeAg-negative chronic HBV infection in indeterminate phase with a low viral load

Objective: To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load. Methods: One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group (n=59) and high HBsAg group (n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results: There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion: The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

Dyslipidemia patterns and associated factors in Wilson's disease patients: a clinical analysis.

This study aims to analyze the lipid metabolism patterns and identify risk factors for dyslipidemia in Wilson's Disease (WD), offering novel insights into diagnosis and treatment strategies for unexplained dyslipidemia. Data from Wilson's disease patients hospitalized at the First People's Hospital of Shanghai from December 2008 to February 2015 were collected. Patients were categorized into normal lipid (46 cases) and dyslipidemia (42 cases) groups based on lipid levels. Group analyzes were conducted using t-tests, chi-square analysis, and rank sum tests. Spearman correlation, multiple linear regression, or Logistic regression were employed to identify relevant influencing factors. 1. The incidence of abnormal blood lipids in a series of Wilson's disease patients was 47.73% (25.12 ± 1.29 years old), and the incidence of control healthy group was 27.40%, with proportions of hypercholesterolemia, hypertriglyceridemia, and low-density lipoprotein cholesterol being 14.77, 30.68, and 29.63%, respectively; 2. Significant differences were observed between the dyslipidemia and normal WD groups in AST/ALT ratio, liver parenchymal echo, liver surface, spleen area, and ultrasound total score.3. Low-and high-density lipoprotein cholesterols (LDL-c and HDL-c) showed no significant correlation with these indicators. Triglyceride (TG) exhibited moderately negative correlation with AST/ALT, liver parenchymal echo, spleen area, and ultrasound score. Total cholesterol (TC) displayed low negative correlation with these factors. 1. Dyslipidemia incidence in Wilson's disease patients may exceed that of the normal population, especially in adolescents with unexplained abnormal lipid metabolism; 2. Patients with mild to moderate liver damage are predisposed to elevated triglycerides and total cholesterol, reflecting liver damage impact on lipid metabolism; 3. Glucose metabolism is not implicated in WD-related dyslipidemia; 4. No significant correlation was found between abnormal lipid metabolism and blood concentration of trace elements in WD patients.

Safety and Effectiveness of a 4-Week Diet on Low-Carb Ready-to-Eat Ketogenic Products as Preoperative Care Treatment in Patients Scheduled for Metabolic and Bariatric Surgery.

Before metabolic and bariatric surgery (MBS), moderate weight loss and liver left lateral section (LLLS) volume reduction are desirable. Low-carb ketogenic diet-induced weight loss before MBS has been shown to have beneficial effects on the reduction in body weight (BW) and LLLS. However, the nutritional protocol of low-carb ketogenic diet may be hard to keep for prolonged periods due to the lack of sweet taste. Furthermore, transitioning to a low-carb ketogenic diet can cause people to crave foods that are restricted in the ketogenic diet, such as cookies, bread, pasta, and bagels. Therefore, many ready-to-eat low-carb ketogenic products (RLCKP) that mimic carbohydrate-rich foods despite a low-carb composition have been provided to make it easier for the patients to adopt a low-carb lifestyle. To date, there are no studies describing the dietary protocol for efficient and safe use of pre-operative RLCKP in terms of weight and LLLS volume reduction in patients with obesity scheduled for MBS. Therefore, the aim of this study was to assess the safety and effectiveness of a 4-week diet using RLCKP in reducing BW and LLLS volume in patients with obesity scheduled for MBS. Patients with obesity (n = 42) with a mean body mass index (BMI) of 42.4 ± 9.2 kg/m2 scheduled for MBS underwent a 4-week preoperative RLCKP diet intervention. Their weight, LLLS volume, and biochemical and metabolic parameters were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. All patients completed the study. We observed highly significant decreases in BW (-6.5%, p < 0.001), and LLLS volume (-22.3%, p < 0.001) and an amelioration of patient clinical status. All patients showed a high frequency of acceptability and compliance in following the diet. No adverse side effects were reported. Based on our findings, we were able to support the hypothesis that a 4-week preoperative RLCKP diet is safe and effective in reducing BW, and LLLS volume in patients with obesity scheduled for MBS.

Design, synthesis and evaluation of novel LpxC inhibitors containing a hydrazone moiety as Gram-negative antibacterial agents

LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To enable the development of novel LpxC inhibitors with potent antibacterial activities, several series of compounds were designed and synthesized and their antibacterial activities were evaluated against E. coli ATCC25922, P. aeruginosa ATCC27853, P. aeruginosa clinical isolate PAE 22-1, K. pneumoniae ATCC700603, K. pneumoniae clinical isolate KPN+22-1 in vitro. Compound 6i exhibited significant antibacterial activities against above five Gram-negative bacteria except P. aeruginosa ATCC27853. Moreover, compound 6i exhibited moderate liver microsomal stability and a promising pharmacokinetic profile (AUC0-t = 1050 ng h mL−1, oral bioavailability of 13.3 %) in Sprague-Dawley rats, acceptable PPB, low risk of drug-drug interactions and non-cytotoxic activity against hepatic cell. Collectively, compound 6i could be a promising Gram-negative antibacterial agent for further investigation.

Down-regulation of miR-29 improves lipid metabolism in fatty liver of dairy cows

In this study, we conducted a thorough investigation into the mechanisms by which miR-29 influences lipid metabolism. Thirty-two cows were selected and categorized into distinct groups based on their liver triglyceride (TG) content: healthy, mild fatty liver, and moderate fatty liver groups. Dairy cows with moderate fatty liver showed higher levels of hepatic lipid accumulation, MDA content and serum AST, ALT and ALP contents and lower hepatic catalase CAT and SOD activities. Subsequently, hepatocytes isolated from healthy calves were exposed to sodium oleate (SO) in the presence or absence of pre-incubation with miR-29 inhibitor or inhibitor NC. Pre-transfection with miR-29 inhibitor resulted in reduced hepatocyte lipid accumulation and MDA levels, as well as decreased levels of AST, ALT, and ALP in the supernatant. In the miR-29 inhibitor + SO group, there was an increase in the expression of SREBP-1, FAS, SCD1, and Sirt1. Meanwhile, the expression of PPARα, CPT1, CPT2, PGC-1α, NRF-1, UCP2, and miR-29 were observed to be decreased. In comparison to the miR-29 inhibitor + SO group, some of the measured indicators showed partial reversal in the miR-29 inhibitor + siSirt1 + SO group. Collectively, these findings provide evidence that miR-29 may play a crucial role in the pathogenesis of fatty liver in dairy cows.

Migraine Management in Medically Complex Patients: a Narrative Review.

The current review aims to provide an overview of migraine treatment strategies in medically complex patients, including those with renal, liver, and cardiovascular disease. In cardiovascular disease, gepants are likely safe for acute therapy; NSAIDs, ergotamines, and triptans are not recommended. Beta-blockers, ACEi/ARBs, and verapamil have potential cardiovascular benefits in addition to migraine preventive benefit. Frovatriptan requires no dose adjustments in kidney disease or in mild to moderate liver disease. Gepants are safe acute and preventive treatment options in mild and moderate renal and hepatic disease. TCAs and valproic acid require no dose adjustments in renal disease. OnabotulinumtoxinA is likely safe in cardiac, renal, and hepatic impairment. Although CGRP monoclonal antibodies are likely safe in renal and hepatic disease, further study is needed in these conditions as well as in cardiac disease, and no dosing recommendations are available. Effective options are available for those with complex medical comorbidities. Further research is required on the safety of newer migraine-specific therapies in these complex populations.

Clinical risk factors for moderate and severe antituberculosis drug-induced liver injury.

To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients.

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0-24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61-0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66-0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97-1.24), p > 0.05) and 2 (ratio 1.03 (0.94-1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.

Thyroid hormone receptor-beta agonists in the treatment of metabolically associated steatotic liver disease. Review

Metabolic dysfunction-associated steatotic liver disease, or metabolically-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, has become the leading chronic liver disease worldwide in the last decade. The spectrum of MASLD ranges from simple hepatic steatosis to metabolic-associated steatohepatitis (MASH), advanced liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Hepatic inflammation and progressive fibrosis are considered to be the most important driving forces for the progression of MASLD/MASH. Therefore, patients with MASH are a key target group for the development of new therapeutic agents. Although many clinical trials have been conducted in patients with MASLD/MASH over the past two decades, until recently there was no licensed drug for the treatment of this very common metabolic liver disease. Preclinical experimental studies and results from human studies have confirmed the importance of thyroid hormone receptor-β (TGR-β) in the development of hepatic steatosis and stimulated interest in the development of TGR-β agonists as potential treatments for MASLD. The effects of TGR-β agonists, mainly resmetirom, on hepatic and cardiometabolic risk factors have been tested in randomized placebo-controlled trials (RCTs) in patients with MASLD/MASH. As a result of the positive data obtained in the phase III RCT (MAESTRO-NASH), the USA FDA agency on March 14, 2024 accelerated approval of the first TGR-β agonist resmetirom as a drug for the treatment of steatohepatitis associated with metabolic dysfunction. Thus, resmetirom has become the first officially approved drug to be recommended in combination with diet and exercise for use in adults with non-cirrhotic MASH with moderate or advanced liver fibrosis (stages F2-F3 fibrosis).

Neural Network Classification Algorithm Based on Self-attention Mechanism and Ensemble Learning for MASLD Ultrasound Images

BackgroundUltrasound image examination has become the preferred choice for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD) due to its non-invasive nature. Computer-aided diagnosis (CAD) technology can assist doctors in avoiding deviations in the detection and classification of MASLD. MethodWe propose a hybrid model that integrates the pre-trained VGG16 network with an attention mechanism and a stacking ensemble learning model, which is capable of multi-scale feature aggregation based on the self-attention mechanism and multi-classification model fusion (Logistic regression, random forest, support vector machine) based on stacking ensemble learning. The proposed hybrid method achieves four classifications of normal, mild, moderate, and severe fatty liver based on ultrasound images. Result and conclusionOur proposed hybrid model reaches an accuracy of 91.34% and exhibits superior robustness against interference, which is better than traditional neural network algorithms. Experimental results show that, compared with the pre-trained VGG16 model, adding the self-attention mechanism improves the accuracy by 3.02%. Using the stacking ensemble learning model as a classifier further increases the accuracy to 91.34%, exceeding any single classifier such as LR (89.86%) and SVM (90.34%) and RF (90.73%). The proposed hybrid method can effectively improve the efficiency and accuracy of MASLD ultrasound image detection.

Impact of pre-existing medical conditions on mortality in geriatric trauma: a nationwide study in Japan.

To investigate the relationship between pre-existing medical conditions and outcomes in elderly trauma patients in Japan. This multicenter observational study utilized data from the Japan Trauma Data Bank (JTDB) from 2019 to 2020. The primary outcome was in-hospital mortality. Factors associated with in-hospital mortality were identified using multivariate logistic regression analysis, from which adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined. Of the participants during the study period, 19,598 patients were included in the analysis. Among the pre-existing medical conditions, moderate or severe liver disease showed the strongest positive association with in-hospital mortality (AOR: 7.087, 95% CI: 3.194-15.722), followed by multiple malignancies (AOR: 3.490, 95% CI: 1.046-11.641), congestive heart failure (AOR: 2.572, 95% CI: 1.920-3.445), and moderate or severe renal disease (AOR: 2.256, 95% CI: 1.584-3.215). Data from JTDB suggests that pre-existing conditions like moderate or severe liver disease, congestive heart failure, and moderate or severe renal disease in elderly trauma patients are positively correlated with in-hospital mortality.

Chelator boosted tumor-retention and pharmacokinetic properties: development of 64Cu labeled radiopharmaceuticals targeting neurotensin receptor.

Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.

Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Proline Henagliflozin in Chinese Subjects with Varying Degrees of Liver Dysfunction.

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel-group, open-label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty-two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long-term safety profile and efficacy have not been specifically studied in this population.

Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment.

99mTc-FGF-2 was tested in vitro and in vivo in mice bearing allografts of sarcoma cells. Images of 99mTc-FGF-2 were acquired using a new portable high-resolution ultra-sensitive gamma camera for small animal imaging. FGF-2 was labeled with high specific activity but low labelling efficiency, thus requiring post-labeling purification by gel-filtration chromatography. In vitro binding to 2C human keratinocytes showed a Kd of 3.36 × 10-9 M. In mice bearing J774A.1 cell allografts, we observed high and rapid tumor uptake of 99mTc-FGF-2 with a high Tumor/Blood ratio at 24 h post-injection (26.1 %ID/g and 12.9 %ID) with low kidney activity and moderate liver activity. we labeled FGF-2 with 99mTc and showed nanomolar Kd in vitro with human keratinocytes expressing FGF-2 receptors. In mice, 99mTc-FGF-2 rapidly and efficiently accumulated in tumors expressing FGF-2 receptors. This new radiopharmaceutical could be used in humans to image TAFs.

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.

A multiple variable index and extracardiac-Fontan associated hepatic fibrosis

BackgroundThe serial follow-up of Fontan-associated liver disease is challenging, as laboratory values are frequently normal, especially with mild to moderate liver disease. ObjectiveWe investigated a composite index's correlation with hepatic biopsy total fibrosis scores in extracardiac Fontan patients. MethodsWe identified extracardiac Fontan patients undergoing cardiac catheterization and transvenous hepatic biopsies between June 2013 and September 2023 and liver shear wave elastography between January 2017 and July 2023. We developed a composite index from the following: 1) elastography values, 2) sex, 3) history of a neonatal aortopulmonary shunt for pulmonary flow obstruction, 4) pacemaker, 5) Fontan duration, 6) bilirubin values, 7) univentricular dysfunction, 8) atrioventricular valvar regurgitation, 9) mean Fontan pressures, and 10) venovenous collaterals presence. We correlated the index with hepatic total fibrosis scores (0–8), the sum of pathology grading (0 to 4) performed for sinusoidal and portal fibrosis. We defined a hepatic total fibrosis score of 0–3 as none to mild and 4–8 as moderate to severe fibrosis. ResultsWe identified 62 patients who underwent 92 transvenous liver biopsies, with 30 patients undergoing 2 biopsies. The average age at biopsy was 15 ± 2 years. We found a strong correlation (rho = 0.8, p = .00001) between liver total fibrosis scores and composite index values. A receiver operating characteristic analysis demonstrated that an index cut-off value of ≥26 predicted a total fibrosis score of ≥4 with a sensitivity of 71 % and a specificity of 75 % (AUC = 0.73, 95 % CI 0.63, 0.83, p = .0001). ConclusionsWe developed a composite index with a moderate predictive ability to discriminate none to mild from moderate to severe hepatic fibrosis. Nevertheless, additional data is needed to assist further validation and determine its clinical utility in the serial follow-up of Fontan associated liver disease.

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

Association of urinary chlorpyrifos, paraquat, and cyproconazole levels with the severity of fatty liver based on MRI

BackgroundThe objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD).MethodsAll participants’ fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples’Hospital. The levels of three urinary pesticides were measured using β-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver.Results53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD.ConclusionThe present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.

Management of a child with portopulmonal hypertension due to cavernous transformation of the portal vein and sple- norenal anastomosis

A clinical case of the development of portopulmonary hypertension in a child after splenorenal anastomosis is presented. The surgical intervention was performed to correct the congenital malformation — cavernous transformation of the portal vein, which led to portal hypertension and varicose veins of the esophagus and stomach. In the long-term postoperative period, pulmonary arterial hypertension, hypersplenism with bilinear cytopenia, and moderate liver failure developed. Combined therapy provided a temporary improvement of the patient status, therefore, during subsequent surgery, the size of the anastomosis was changed. This led to a sustained decrease in pulmonary artery blood pressure and clinical improvement in the boy’s condition.