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Background: Serum level of microRNA-122 (miR-122) has been reported as a sensitive diagnostic biomarker for detecting liver injury, comparable to the aminotransferases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities are increased in other conditions, such as acute skeletal muscle injury (ASMI). We determined whether miR-122 is nonspecifically increased in patients suffering from ASMI., Methods: We measured ALT, AST, creatine kinase (CK), and miR-122 in 3 groups: healthy controls (n = 24), patients with ASMI (total n = 29, 11 with recreational drug use and 18 without recreational drug use), and patients with acute liver injury (ALI; n = 14)., Results: Levels of ALT, AST, and CK increased 83%, 97%, and 100% for patients with ASMI and 100% for all 3 enzymes in ALI patients. In contrast, miR-122 increased in 34% of patients with ASMI (44.4% with recreational drug use and 18.2% without recreational drug use) and 100% of ALI patients. In 2 drug-induced liver injury cases, miR-122 increased about 12-24 hours before ALT and AST., Conclusion: Recreational drug misuse is associated with both rhabdomyolysis and drug-induced liver injury (DILI). The traditional liver function markers AST and ALT were nonspecifically increased in the majority of patients with ASMI. miR-122 is only increased in patients at risk for DILI and demonstrates superior specificity for liver injury., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure., Methods: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes., Results: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01)., Conclusions: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD., Methods: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD., Results: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up., Conclusions: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication., Methods: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data., Results: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end., Conclusion: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite its high prevalence, there are no medications currently approved by the Food and Drug Administration for the treatment of NAFLD. Recent work has suggested that NAFLD has a strong genetic component and identifying causative genes will improve our understanding of the molecular mechanisms contributing to NAFLD and yield targets for future therapeutic investigations. Oxidative stress is known to play an important role in NAFLD pathogenesis, yet the underlying mechanisms accounting for disturbances in redox status are not entirely understood. To better understand the relationship between the glutathione redox system and signs of NAFLD in a genetically-diverse population, we measured liver weight, serum biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and graded liver pathology in a large cohort of Diversity Outbred mice. We compared hepatic endpoints to those of the glutathione redox system previously measured in the livers and kidneys of the same mice, and we screened for statistical and genetic associations using the R/qtl2 software. We discovered several novel genetic loci associated with markers of liver health, including loci that were associated with both liver steatosis and glutathione redox status. Candidate genes within each locus point to possible new mechanisms underlying the complex relationship between NAFLD and the glutathione redox system, which could have translational implications for future studies targeting NAFLD pathology., Competing Interests: Declaration of competing interest none., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023. Published by Elsevier B.V.)

The consumption of mushrooms containing α-Amanitin (α-A) can lead to severe liver damage. In this study, toxicological experiments were conducted to confirm the protective effects of pomegranate seed oil (PSO) and black cumin oil (BCO) against α-A-induced hepatotoxicity. Rats exposed once to α-A (3 mg/kg bw, i.p.) or saline alone (0.1 ml, i.p.) were either left untreated or treated with PSO or BCO at a dose of 2 ml/kg bw/day by oral gavage on the same day, and the treatment was continued for 7 days. Serum aminotransferases (ALT and AST), alkaline phosphatase (ALP) and total protein levels were measured and the active caspase 3 (cl-caspase 3) was evaluated by western blotting in the liver. Serum ALT, AST and ALP levels tended to decrease in the α-A exposed group, but no statistically significant difference was found compared to the saline group (p > 0.05). PSO and BCO did not affect serum liver function tests in rats exposed to saline or α-A. α-A toxicity was demonstrated by a significant decrease in serum total protein level (p < 0.05), a significant increase in liver cl-caspase 3 expression (p < 0.05), and structural liver damage mainly characterized by mononuclear inflammation and steatosis. When α-A exposed rats were treated with BCO, the increase in cl-caspase 3 was not inhibited, on the contrary BCO increased cl-caspase 3 in healthy rats (p < 0.05). PSO significantly ameliorated α-A-induced cl-caspase 3 increase and inflammatory histopathology in the liver. Both PSO and BCO completely prevented α-A-induced protein degradation. The findings indicate that PSO and BCO may protect liver functions against α-A-induced hepatotoxicity, encouraging future comprehensive studies to test them at different doses and frequency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

BACKGROUND Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. CASE REPORT We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. CONCLUSIONS The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E.

Background: There is a contradiction in the use of microbiota-therapies, including probiotics, prebiotics, and synbiotics, to improve the condition of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this review was to evaluate the effect of microbiota-therapy on liver injury, inflammation, and lipid levels in individuals with NAFLD., Methods: Using Pubmed, Embase, Cochrane Library, and Web of Science databases were searched for articles on the use of prebiotic, probiotic, or synbiotic for the treatment of patients with NAFLD up to March 2024., Results: Thirty-four studies involving 12,682 individuals were included. Meta-analysis indicated that probiotic, prebiotic, and synbiotic supplementation significantly improved liver injury (hepatic fibrosis, SMD = -0.31; 95% CI: -0.53, -0.09; aspartate aminotransferase, SMD = -0.35; 95% CI: -0.55, -0.15; alanine aminotransferase, SMD = -0.48; 95% CI: -0.71, -0.25; alkaline phosphatase, SMD = -0.81; 95% CI: -1.55, -0.08), lipid profiles (triglycerides, SMD = -0.22; 95% CI: -0.43, -0.02), and inflammatory factors (high-density lipoprotein, SMD = -0.47; 95% CI: -0.88, -0.06; tumour necrosis factor alpha, SMD = -0.86 95% CI: -1.56, -0.56)., Conclusion: Overall, supplementation with probiotic, prebiotic, or synbiotic had a positive effect on reducing liver enzymes, lipid profiles, and inflammatory cytokines in patients with NAFLD., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population with no effective drug treatments available. Previous animal studies reported that a polyphenol-rich extract from the Amazonian berry camu-camu (CC) prevented hepatic steatosis in a mouse model of diet-induced obesity. This study aims to determine the impact of CC on hepatic steatosis (primary outcome) and evaluate changes in metabolic and gut microbiota profiles (exploratory outcomes). A randomized, double-blind, placebo-controlled crossover trial is conducted on 30 adults with overweight and hypertriglyceridemia, who consume 1.5 g of CC capsules or placebo daily for 12 weeks. CC treatment decreases liver fat by 7.43%, while it increases by 8.42% during the placebo intervention, showing a significant difference of 15.85%. CC decreases plasma aspartate and alanine aminotransferases levels and promotes changes in gut microbiota composition. These findings support that polyphenol-rich prebiotic may reduce liver fat in adults with overweight, reducing the risk of developing NAFLD., Competing Interests: Declaration of interests A. Morissette, L.D., and T.G. received studentship from Fonds de recherche du Québec – Santé (FRQS). A.-L.A. is supported by the Fondation du Centre Hospitalier Universitaire de Québec. A. Marette holds a Pfizer/CIHR Partnered Research Chair on the pathogenesis of insulin resistance and cardiovascular diseases. Y.D. holds an NSERC-Diana Food Industrial Partnership Chair on prebiotic effects of polyphenols. M.-C.V. is the recipient of a Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health. A.-M.C. and C.G. received a career award from the FRQS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and β-cell function in middle-aged Japanese individuals, whose BMI averaged < 23.0 kg/m 2 . Pancreatic β-cell function was assessed using the disposition index calculated by a product of the insulinogenic index (IGI) and Matsuda insulin sensitivity index, a biomarker of early-phase glucose-stimulated insulin secretion and whole-body insulin sensitivity, respectively. Multivariate linear regression analyses revealed that the disposition index was associated inversely with GGT independently of percentage trunk fat, homeostasis model assessment insulin resistance (HOMA-IR), a marker of insulin resistance, and Matsuda index. When IGI was included instead of the disposition index, IGI (inversely) and HOMA-IR were associated with GGT independently of percentage trunk fat and Matsuda index. When the area under the glucose concentration curve (AUCg) during an oral glucose tolerance test was included instead of the disposition index, AUCg and HOMA-IR emerged as independent determinants of GGT. ALT/AST was associated with HOMA-IR alone. Results suggest a different pathophysiologic basis between GGT and ALT/AST in predicting diabetic risk in non-obese Japanese., (© 2024. The Author(s).)

Aim: Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Broad-spectrum antibiotics are used to treat it. However, due to antibiotic resistance, alternative treatments are needed. Mesenchymal stem cells (MSCs) have become a promising therapeutic tool for sepsis due to their immunomodulatory properties. The limitations of MSC therapy have led to increased attention to cell derivatives such as conditioned medium (CM). This study investigates the immunomodulatory effects of young and old MSC-CM during the inflammatory phase of sepsis., Main Methods: The cecal ligation and puncture (CLP) model was used to induce sepsis in mice. The mice were divided into four groups: sham, CLP, CLP treated with young MSC-CM, and CLP treated with old MSC-CM. The CM was injected intraperitoneally at 2-, 12-, and 24-hours post-surgery. After 72 h, blood was collected and white blood cells (WBCs) were counted. In addition, serum and tissue were isolated, and the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in serum, bacterial load in the spleen, concentration of pro- and anti-inflammatory cytokines, and histopathology of liver and lung were investigated., Key Findings: MSC-CM decreased serum AST and ALT levels, bacterial load in the spleen, and pro-inflammatory cytokines in serum. In addition, tissue damage was reduced, and the survival rate and WBC count increased. There was no significant difference between the young and old MSC-CM., Significance: MSC-CM effectively reduced inflammation-induced tissue damage in the liver and lungs during sepsis. Although young MSC-CM had better immunomodulatory effects than old MSC-CM, the difference was not significant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09-1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04-1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11-1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21-1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20-3.75), p < 0.001) were associated hyperferritinemia. The log 10 value of HBV or HCV viral load was not associated with the log 10 value of ferritin level (Spearman's rank correlation coefficient: - 0.025, p = 0.81 and 0.002, p = 0.92). In conclusion, host factors, rather than viral factors, are associated with hyperferritinemia in patients with HCV., (© 2024. The Author(s).)

Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load., Methods: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels., Results: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients., Conclusion: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression., (© 2024. The Author(s).)

Purpose: This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression., Method: Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1., Results: After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05)., Conclusion: For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm -1 (COONa vibrations) and increased CH 2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl 4 ). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl 4 -induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury., (© 2024. The Author(s).)

Background: The presence and severity of liver fibrosis are important prognostic variables when evaluating people with chronic hepatitis C (CHC). Although liver biopsy remains the reference standard, non-invasive serological markers, such as the four factors (FIB-4) score and the Forns index, can also be used to stage liver fibrosis., Objectives: To determine the diagnostic accuracy of the FIB-4 score and Forns index in staging liver fibrosis in people with chronic hepatitis C (CHC) virus, using liver biopsy as the reference standard (primary objective). To compare the diagnostic accuracy of these tests for staging liver fibrosis in people with CHC and explore potential sources of heterogeneity (secondary objectives)., Search Methods: We used standard Cochrane search methods for diagnostic accuracy studies (search date: 13 April 2022)., Selection Criteria: We included diagnostic cross-sectional or case-control studies that evaluated the performance of the FIB-4 score, the Forns index, or both, against liver biopsy, in the assessment of liver fibrosis in participants with CHC. We imposed no language restrictions. We excluded studies in which: participants had causes of liver disease besides CHC; participants had successfully been treated for CHC; or the interval between the index test and liver biopsy exceeded six months., Data Collection and Analysis: Two review authors independently extracted data. We performed meta-analyses using the bivariate model and calculated summary estimates. We evaluated the performance of both tests for three target conditions: significant fibrosis or worse (METAVIR stage ≥ F2); severe fibrosis or worse (METAVIR stage ≥ F3); and cirrhosis (METAVIR stage F4). We restricted the meta-analysis to studies reporting cut-offs in a specified range (+/-0.15 for FIB-4; +/-0.3 for Forns index) around the original validated cut-offs (1.45 and 3.25 for FIB-4; 4.2 and 6.9 for Forns index). We calculated the percentage of people who would receive an indeterminate result (i.e. above the rule-out threshold but below the rule-in threshold) for each index test/cut-off/target condition combination., Main Results: We included 84 studies (with a total of 107,583 participants) from 28 countries, published between 2002 and 2021, in the qualitative synthesis. Of the 84 studies, 82 (98%) were cross-sectional diagnostic accuracy studies with cohort-based sampling, and the remaining two (2%) were case-control studies. All studies were conducted in referral centres. Our main meta-analysis included 62 studies (100,605 participants). Overall, two studies (2%) had low risk of bias, 23 studies (27%) had unclear risk of bias, and 59 studies (73%) had high risk of bias. We judged 13 studies (15%) to have applicability concerns regarding participant selection. FIB-4 score The FIB-4 score's low cut-off (1.45) is designed to rule out people with at least severe fibrosis (≥ F3). Thirty-nine study cohorts (86,907 participants) yielded a summary sensitivity of 81.1% (95% confidence interval (CI) 75.6% to 85.6%), specificity of 62.3% (95% CI 57.4% to 66.9%), and negative likelihood ratio (LR-) of 0.30 (95% CI 0.24 to 0.38). The FIB-4 score's high cut-off (3.25) is designed to rule in people with at least severe fibrosis (≥ F3). Twenty-four study cohorts (81,350 participants) yielded a summary sensitivity of 41.4% (95% CI 33.0% to 50.4%), specificity of 92.6% (95% CI 89.5% to 94.9%), and positive likelihood ratio (LR+) of 5.6 (95% CI 4.4 to 7.1). Using the FIB-4 score to assess severe fibrosis and applying both cut-offs together, 30.9% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the FIB-4 score when used for assessing significant fibrosis (≥ F2) and cirrhosis (F4) in the main review text. Forns index The Forns index's low cut-off (4.2) is designed to rule out people with at least significant fibrosis (≥ F2). Seventeen study cohorts (4354 participants) yielded a summary sensitivity of 84.7% (95% CI 77.9% to 89.7%), specificity of 47.9% (95% CI 38.6% to 57.3%), and LR- of 0.32 (95% CI 0.25 to 0.41). The Forns index's high cut-off (6.9) is designed to rule in people with at least significant fibrosis (≥ F2). Twelve study cohorts (3245 participants) yielded a summary sensitivity of 34.1% (95% CI 26.4% to 42.8%), specificity of 97.3% (95% CI 92.9% to 99.0%), and LR+ of 12.5 (95% CI 5.7 to 27.2). Using the Forns index to assess significant fibrosis and applying both cut-offs together, 44.8% of people would obtain an indeterminate result, requiring further investigations. We report the summary accuracy estimates for the Forns index when used for assessing severe fibrosis (≥ F3) and cirrhosis (F4) in the main text. Comparing FIB-4 to Forns index There were insufficient studies to meta-analyse the performance of the Forns index for diagnosing severe fibrosis and cirrhosis. Therefore, comparisons of the two tests' performance were not possible for these target conditions. For diagnosing significant fibrosis and worse, there were no significant differences in their performance when using the high cut-off. The Forns index performed slightly better than FIB-4 when using the low/rule-out cut-off (relative sensitivity 1.12, 95% CI 1.00 to 1.25; P = 0.0573; relative specificity 0.69, 95% CI 0.57 to 0.84; P = 0.002)., Authors' Conclusions: Both the FIB-4 score and the Forns index may be considered for the initial assessment of people with CHC. The FIB-4 score's low cut-off (1.45) can be used to rule out people with at least severe fibrosis (≥ F3) and cirrhosis (F4). The Forns index's high cut-off (6.9) can be used to diagnose people with at least significant fibrosis (≥ F2). We judged most of the included studies to be at unclear or high risk of bias. The overall quality of the body of evidence was low or very low, and more high-quality studies are needed. Our review only captured data from referral centres. Therefore, when generalising our results to a primary care population, the probability of false positives will likely be higher and false negatives will likely be lower. More research is needed in sub-Saharan Africa, since these tests may be of value in such resource-poor settings., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Gastroesophageal reflux disease (GERD) is a common condition worldwide. Despite numerous studies on GERD, the causal relationships between blood/urine metabolites and GERD remain unclear. This study aims to explore the causal relationships between GERD and 35 blood/urine metabolites. In this study, we conducted Mendelian randomization (MR) analyses for 35 blood/urine metabolites with GERD phenotypes from the FinnGen R10 and UKB databases separately. We then performed a meta-analysis of the inverse variance weighted results from the 2 MR analyses and applied multiple corrections to the significant P values from the meta-analysis. Finally, we conducted reverse causality validation for the corrected positive blood/urine metabolite phenotypes with GERD. After conducting MR analysis combined with meta-analysis and performing multiple corrections, we found significant positive causal associations between only 3 blood/urine metabolites and GERD, with no significant reverse associations. Among them, 2 are risk factors for the occurrence of GERD: alanine aminotransferase levels (odds ratio (OR) = 1.120, 95% confidence interval (CI) = 1.064-1.180, P = .0005) and urate levels (OR = 1.095, 95% CI = 1.044-1.147, P = .005). Additionally, sex hormone-binding globulin levels are protective against GERD (OR = 0.928, 95% CI = 0.896-0.961, P = .0009). Elevated levels of the metabolites alanine aminotransferase and urate are associated with an increased risk of GERD, identifying them as risk factors for the condition. In contrast, higher levels of SHBG are linked to a decreased risk of GERD, indicating that SHBG is a protective factor against the disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain., Methods: Metabolic phenotypes and outcomes associated with ERLIN1 p.Ile291Val were analyzed by using a genome-first approach in the UK Biobank (UKB), Penn Medicine BioBank (PMBB), and All of Us cohort., Findings: ERLIN1 p.Ile291Val carriers exhibited significantly lower serum levels of alanine aminotransferase and aspartate aminotransferase as well as higher levels of triglycerides, low-density lipoprotein cholesterol, Apolipoprotein B, high-density lipoprotein cholesterol, and Apolipoprotein A1 in UKB, and these values were affected by ERLIN1 p.Ile291Val in an allele-dose-dependent manner. Homozygous ERLIN1 p.Ile291Val carriers had a significantly reduced risk of developing metabolic dysfunction-associated SLD (MASLD, adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI], 0.88-0.96). The protective effect of this variant was enhanced in patients with alcoholic liver disease. Our results were replicated in PMBB and the All of Us cohort. Strikingly, the protective effects of ERLIN1 p.Ile291Val were not apparent in individuals carrying the TM6SF2 p.Glu167Lys variant associated with increased risk of SLD. We analyzed the effects of predicted loss-of-function ERLIN1 variants and found that they had opposite effects, namely reduced plasma lipids, suggesting that ERLIN1 p.Ile291Val may be a gain-of-function variant., Conclusion: Our study contributes to a better understanding of ERLIN1 by investigating a coding variant that has emerged as a potential gain-of-function mutation with protective effects against MASLD development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed., Methods: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili)., Results: No differences were observed in baseline LFTs across groups (all, p > 0.25, η 2 < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η 2 < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, η p 2 < 0.03), no effect of ILE type (all p > 0.60, η p 2 < 0.03), and no effect of time (all p > 0.69, η p 2 < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η 2 < 0.04)., Conclusion: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period.

The optimal frequency and timing of laboratory monitoring during isotretinoin treatment remains controversial. We aimed to investigate the frequency, timing, and severity of abnormal results during isotretinoin for acne. We conducted a retrospective cohort study comprising 444 acne patients prescribed isotretinoin at Boston Medical Center from 2004 to 2017; these patients had at least one available baseline laboratory result. We categorized patients into two groups: group A (normal values at baseline and during the first 2 months of isotretinoin therapy) and group B (abnormal values at baseline or during the first 2 months of isotretinoin therapy) and assessed the laboratory values after 2 months. The frequency of abnormal results for triglycerides, cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 2 months for patients in group A was 21.1%, 13.6%, 8.8%, and 6.0%, respectively, with very rare grade 2 (moderate) or higher abnormalities. In contrast, the frequency of abnormal results for patients in group B for triglycerides, cholesterol, AST, and ALT was higher at 67.9%, 88.0%, 40.0%, and 25.0%, respectively ( P < 0.05, except for ALT). No patient developed higher than grade 1 (mild) complete blood count (CBC) abnormality. This study proposed that healthy patients with normal results at baseline and during the first 2 months of isotretinoin therapy might not need routine monitoring after month 2 of medication. Routine monitoring of CBC is not necessary.

The study aimed to investigate the effect of the aqueous extract of the chamomile plant on oxidative stress induced by procyclidine in rats. 30 rats were randomly divided into five groups, with 6 rats in each group. The first group was given distilled water only, while the second group was administered procyclidine (1 mg/kg body weight) in three doses daily for a period of 60 days. The third group was given procyclidine in the same doses as the second group for 30 days. Afterward, they were administered an aqueous extract of chamomile (300 mg/kg) for another 30 days. The fourth group was administered the aqueous extract (300 mg/kg) for 30 days. Subsequently, they were given procyclidine in the same doses as the second group for another 30 days. On the other hand, the fifth group was administered the aqueous extract of chamomile (300 mg/kg) for a period of 60 days to investigate the potential effects of the extract. Afterward, blood samples were drawn to measure various biological parameters, including Total Oxidant Status (TOS), Malondialdehyde (MDA), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Acetylcholinesterase (AChE) activity. Finally, an anatomical study was conducted on the kidneys, brain, and liver to enhance the research. The results displayed a significant increase in the levels of TOS, MDA, AST, ALT enzymes, and Ach-E activity in the second group compared to the first group. Groups 3 and 4 significantly decreased compared to the second group based on the same standards. In regard to Group 5, there are no significant moral differences between it and Group 1. Finally, this study demonstrated the importance of using chamomile extract as an antioxidant and its potential in cancer prevention against the oxidative stress induced by excessive doses of procyclidine. (p ≤ 0.005).

Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking., Aim: To assess whether it is beneficial to undergo a prolonged flare after NA cessation., Methods: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward., Results: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group., Conclusions: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms., Method: We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage., Result: We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (β = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (β = -0.21; 95% CI: -0.39, -0.03), Mn and the annual increase rate of GLB (β = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (β = -1.15; 95% CI: -2.00, -0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways., Conclusion: Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The aim of this meta-analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random-effects models with DerSimonian-Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD., (© 2024 John Wiley & Sons Ltd.)

Scope: Long-term consumption of excessive dietary advanced glycation end-products such as N ε -carboxymethyl-lysine (CML), which are produced by the Maillard reaction during food thermal processing, leads to nonalcoholic fatty liver disease (NAFLD) along with high fat consumption. The study previously finds that administration of Lactococcus lactis KF140 (LL-KF140) detoxifies CML by decreasing CML absorption both in a rat model and clinical trial., Methods and Results: The present study evaluates the ameliorative effect of LL-KF140 on NAFLD and fatty liver-related biomarkers in a mouse model induced by CML and high fat. LL-KF140 is orally administered to mice at a concentration of 1 × 10 7 or 1 × 10 8 colony-forming unit (CFU) per mouse for 8 weeks. LL-KF140 administration ameliorates the NAFLD-related symptoms by reducing body weight and fat mass gain along with levels of serum aspartate transaminase, alanine transferase, and lipids as well as glucose intolerance and insulin resistance in CML-treated mice. In addition, histological analysis including staining and western blotting shows that LL-KF140 suppresses the lipogenesis pathway and CML absorption, thereby suppressing CML-induced NAFLD., Conclusion: These findings suggest that LL-KF140 attenuates dietary CML-induced NAFLD by suppressing the de novo lipogenesis pathway, and it may be used as a probiotic strain., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

The structure and bioactivities of a novel polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit (THP-3) were investigated. The crude polysaccharides of Turcz. ex Herd. (THP) were extracted by hot water extraction. After purification, the chemical structure of polysaccharides was identified. Then, a mouse model of acute drug-induced liver injury was constructed using 4-acetamidophenol (APAP) and pretreated with THP. The number-average molecular weight of THP-3 was 48.89 kDa and the mass average molar mass was 97.87 kDa. THP-3 was mainly composed of arabinose (42.54 %), glucose (27.62 %), galacturonic acid and galactose (29.84 %). The main linkage types of THP-3 were 1-linked Araf, 1,4-linked Glcp, and 1,3,6-linked Galp. In addition, after THP treatment, serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGT) in AILI mice were successfully down-regulated. The results showed that THP could prevent the characteristic morphological changes of hepatic lobular injury and lipid depletion caused by APAP, reduced the level of oxidative damage in mice, increased the expression of APAP-induced hypolipidemia and related inflammatory indicators, and improved the detoxification function of liver. In general, the newly extracted THP polysaccharide has a good liver protection effect and is an ideal natural medicine for the treatment of liver diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease., Methods: Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated., Results: FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs., Conclusion: FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period., (© 2024. The Author(s).)

Objective: Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD., Materials and Methods: This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS., Results: In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers ( p  < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors., Conclusions: In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD.

Background & Aims: Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term HBsAg seroclearance after entecavir cessation., Methods: This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance., Results: A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p <0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p <0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed., Conclusions: The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption., Impact and Implications: Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data., Methods: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD., Results: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L., Conclusions: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: There is a lack of data on the impact of donor liver function tests (LFTs) on pancreas transplantation outcomes. Understanding their contribution could expand the donor pool., Methods: Using the UNOS database, data from January 2010-2022 was retrospectively analyzed. Multivariable cox regressions were performed to evaluate the association between LFTs (AST, ALT and total bilirubin levels), graft failure and mortality up to three years post-transplant., Results: 9138 pancreas transplants were completed. Multivariate analysis showed no association between donor AST values > 500 U/L and increased rates of graft failure (p = 0.826) or mortality (p = 0.836). Similar findings were noted for donor ALT values > 500 U/L (p = 0.522 and p = 0.997, respectively). There was no correlation with graft failure (p = 0.322) or mortality (p = 0.423) for total bilirubin levels >3 mg/dL., Conclusion: LFTs in the deceased pancreas donor did not increase risk of graft failure or mortality following pancreas transplantation. Elevated LFTs should not serve as absolute contraindications to transplant., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH., Methods: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis., Results: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival., Conclusion: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose., Impact and Implications: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Identification of abdominal injury (AI) in children with concern for physical abuse is important, as it can provide important medical and forensic information. Current recommendations are to obtain screening liver function tests (LFTs) in all children with suspected physical abuse and an abdominal computed tomography (CT) when the aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is >80 IU/L. This threshold to obtain an abdominal CT is lower than general trauma guidelines, which use a cutoff of AST >200 IU/L or ALT >125 IU/L., Methods: This was a retrospective review of children aged 0 to 60 months at a single pediatric tertiary care center who were evaluated for physical abuse and had AST or ALT >80 IU/L. Subjects were then stratified into two groups: midrange (AST ≤200 IU/L and ALT ≤125 IU/L) and high-range (AST >200 IU/L and/or ALT >125 IU/L) LFTs., Results: Abdominal CTs were performed in 55% (131 of 237) of subjects, 38% (50 of 131) with midrange LFTs and 62% (81 of 131) with high-range LFTs. Abdominal injury was identified in 19.8% (26 of 131) of subjects. Subjects with AI were older than those without AI (mean [SD] age, 18.7 [12.5] vs. 11.6 [12.2] months; p = 0.009). The highest yield of abdominal CTs positive for AI was in the group with high-range LFTs with signs or symptoms of AI at 52.0% (13 of 25; 95% confidence interval, 31.3-72.2%). The negative predictive value of having midrange LFTs and no signs or symptoms of AI was 100% (95% confidence interval, 97.0-100%)., Conclusion: Our data suggest that abdominal CT may not be necessary in children being evaluated for physical abuse who have AST ≤200 IU/L and ALT ≤125 IU/L and do not have signs or symptoms of AI. This could limit the number of abdominal CTs performed., Level of Evidence: Diagnostic Test/Criteria; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with psoriasis are at increased risk of liver function abnormalities., Objective: Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis., Methods: Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY)., Results: 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline., Limitations: Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction., Conclusion: Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods., Competing Interests: Conflicts of interest ML: Employee of Mount Sinai and receives research funds from Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly and Company, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Pfizer, Sanofi-Regeneron, and UCB Pharma; consultant for Almirall, AltruBio Inc., AnaptysBio, Apogee, Arcutis Inc., AstraZeneca, Atomwise, Avotres Therapeutics, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, EPI, Evommune Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi, and Verrica. JFM: Consultant and/or investigator for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. BS: Consultant (honoraria) for AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly and Company, Evelo Biosciences, Immunic Therapeutics, Janssen, Kangpu Pharmaceuticals, LEO Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Monte Carlo, Novartis, Pfizer, Protangonist, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda/Nimbus, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; stock options from Connect Biopharma, Mindera Health; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly and Company, Incyte, Janssen, Regeneron, and Sanofi Genzyme; Scientific Co-Director (consulting fee) for CorEvitas Psoriasis Registry; Investigator for CorEvitas Psoriasis Registry; Editor-in-Chief (honorarium) for Journal of Psoriasis and Psoriatic Arthritis. AA: Research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, EPI, Incyte, Janssen, LEO Pharma, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. AY: No conflicts of interest to disclose; PG: Consultant for AbbVie, Abiogen, Almirall, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB Pharma; BS, LP, DdC, NC, OD: Employees and shareholders of UCB Pharma. ABG: Honoraria as an advisory board member and consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, DiCE Therapeutics, Eli Lilly and Company, Janssen, Novartis, Sanofi, UCB Pharma, and XBiotech; research/educational grants from AnaptysBio, Bristol Myers Squibb, Highlights Therapeutics, Janssen, MoonLake Therapeutics, Novartis, and UCB Pharma; all funds go to Mount Sinai Medical School., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Nutritional status during pregnancy can impact fetal development, yet less is known about how alcohol may interact with nutritional status to influence infant outcomes. Pregnant women (n=196) completed 2, 24-hour dietary recalls and provided a venous blood sample to be analyzed for liver enzymes (GGT -gamma-glutamyl transferase; ALT -alanine transaminase; and AST -aspartate transferase), iron, ferritin, and zinc concentrations. Infants were assessed at 6 weeks of age. Women who consumed alcohol had significantly higher ferritin levels compared to non-drinkers (51.8 vs. 34.2). While 44% of women had ferritin <30 ug/L (an indicator of iron deficiency), and 24% of women were low in serum iron, and 72% were low in serum zinc. All six drinking measures for 1st trimester and previous week were significantly correlated with GGT and AST levels while 4 out of 6 alcohol measures were associated with levels of ALT and ferritin. At six weeks of age, nearly all physical measures differentiated infants with alcohol exposure from infants without exposure. Controlling for six covariates, maternal ferritin was significantly and inversely associated with infant head circumference (OFC) centile among infants with alcohol exposure. GGT was inversely associated with infant height and weight centile among unexposed infants. Seventy-four percent (74%) of mothers who consumed alcohol were found to be low in serum zinc, yet higher maternal zinc was associated with more dysmorphology. This may indicate that higher zinc status is not protecting the fetus from the teratogenic effects of alcohol. Prenatal alcohol exposure, ferritin, and zinc status influence infant growth and neurodevelopment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of the present clinical trial was to determine the impact of zinc supplementation on serum liver enzymes, steatosis severity, lipid profile, and inflammatory status in overweight or obese children with nonalcoholic steatohepatitis (NASH). This randomized controlled trial was conducted by enrolling 60 children with NASH, aged 10-18 years old. The participants were randomly assigned to two groups that received either 30 mg/day of elemental zinc or placebo for 16 weeks. The severity of liver steatosis was evaluated using liver ultrasonography. Fasting blood samples were collected from each patient at the beginning and after 16 weeks of intervention to measure biochemical parameters. Following a 16-week intervention, zinc supplementation compared with placebo significantly decreased serum alanine aminotransferase (ALT) concentrations and high-sensitivity C-reactive protein and considerably enhanced HDL-cholesterol values. However, zinc intake had no considerable impact on aspartate aminotransferase, the severity of liver steatosis, anthropometric parameters, and other lipid indices versus the placebo group. Overall, zinc supplementation showed a promising impact on serum ALT, HDL-cholesterol, and inflammatory status in overweight or obese children suffering from NASH. Zinc supplementation may be a new strategy for the amelioration of NASH in overweight or obese children. This trial has been registered on the Iranian website for registration of clinical trials with the special ID of IRCT20200531047614N1 ( https://www.irct.ir/trial/48543 )., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Many children with Wilson's disease are complicated with dyslipidemia. The aim of this study was to investigate the risk factors for the development of fatty liver disease (FLD) in children with Wilson's disease., Methods: We evaluated sex, age, weight, the disease course, treatment course, clinical classification, alanine transaminase (ALT), aspartate transaminase, γ-glutamyl transpeptidase, total biliary acid, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, uric acid, fibrinogen (FBG), creatinine, procollagen III N-terminal propeptide, laminin, hyaluronic acid, type IV collagen, and performed receiver operating characteristic curve analysis to investigate the forecast value of individual biochemical predictors and combined predictive indicators to evaluate FLD in Wilson's disease., Results: The multivariate logistic regression analysis revealed that ALT [odds ratio (OR), 1.011; 95% confidence interval (CI), 1.004-1.02; P  = 0.006], uric acid (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017), FBG (OR, 3.668; 95% CI, 1.145-13.71; P  = 0.037), creatinine (OR, 0.872; 95% CI, 0.81-0.925; P  < 0.001), and laminin (OR, 1.01; 95% CI, 1.002-1.018; P  = 0.017) acted as independent risk factors in Wilson's disease complicated with FLD. The receiver operating characteristic curves for combined predictive indicators demonstrated an area under the curve values of 0.872, which was found to be a significant predictors for FLD in Wilson's disease., Conclusions: We screened out the most important risk factors, namely ALT, uric acid, creatinine, FBG, and laminin for Wilson's disease complicated with FLD. The joint prediction achieved is crucial for identifying children with Wilson's disease complicated with FLD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (P interaction  = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10-20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients' serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis., (© 2024. The Author(s).)

Introduction: A novel indicator of inflammation is the systemic immune-inflammation index (SII), and liver dysfunction is linked to the advancement of inflammation. In light of this, this study aims to look into any potential connections between SII and markers of liver injury., Methods: A cross-sectional study was conducted using the National Health and Nutrition Examination (NHANES) dataset for 2017-2020. The linear relationship between SII and markers of liver injury was examined using multiple linear regression models. Examining threshold effects and fitted smoothed curves were utilized to describe nonlinear connections., Results: A total of 8213 adults aged 18-80 years participated in this population-based study. In the fully adjusted model, SII maintained a negative association with ALT(β = -0.003, 95%CI:-0.005, -0.002, P<0.00001), AST(β = -0.004, 95% CI:-0.005, -0.002, P<0.00001), and GGT(β = -0.004, 95% CI:-0.007, -0.000, P = 0.03791) and a positive association with ALP (β = 0.005, 95% CI:0.003, 0.007, P<0.00001). In subgroup analyses, it was found that SII remained negatively correlated with ALT, AST and GGT in gender, age and body mass index. SII was positively correlated with ALP at BMI≥25(kg/m2)(β = 0.005, 95% CI:0.003, 0.008, P = 0.00001), and was negatively correlated with ALT(β = -0.004, 95% CI:-0.005, -0.002, P<0.00001), AST(β = -0.004, 95% CI:-0.005, -0.003, P<0.00001) and GGT(β = -0.004, 95% CI:-0.008, -0.000, P = 0.02703) at BMI≥25, whereas no significant correlation was observed at BMI<25 (all P-values>0.05). Furthermore, the association between SII and markers of liver injury was nonlinear. By using a two-stage linear regression model for analysis, a U-shaped relationship was found to exist between SII and ALT with a turning point of 818.40(1,000 cells/μl). The inflection points of SII with AST and GGT were 451.20 (1,000 cells/μl) and 443.33 (1,000 cells/μl), respectively, and no significant inflection point with ALP was observed. Interaction tests demonstrated that SII correlation with ALT, AST, ALP, and GGT was not significantly different between strata (all p for interaction>0.05)., Conclusions: The research findings suggested that there was a negative correlation between SII and ALT, AST and GGT, and a positive correlation with ALP. However, larger prospective investigations are still greatly needed to confirm the findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang, Qin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation., Hypothesis/purpose: This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial., Study Design: A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24., Results: Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (β, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (β, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (β, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid., Conclusion: Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Glac Biotech Co., Ltd. provided financial support in the form of salaries for [J.-H.L., C.-H.L., Y.-W.K., J.-F.C., S.-Y.T., C.-M.L., Y.-C.H., Y.-Y.H., K.-C.H., H.-H.H.], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known., Methods: We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD., Results: A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases., Conclusion: There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD., (© 2024. The Author(s).)

Background: Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance., Methods: In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects., Results: The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L., Conclusions: There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)