Liver Enzymes Research Articles

Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand

BACKGROUND Thus far, genetic analysis of patients clinically diagnosed with glycogen storage diseases (GSDs) in Thailand has not been reported. AIM To evaluate the clinical and biochemical profiles, molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD. METHODS Children aged < 18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited. Whole-exome sequencing (WES) was performed to identify the causative gene variants. Medical records were assessed. RESULTS All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia (n = 1), III (n = 3), VI (n = 3), and IX (n = 1). A total number of 10 variants were identified including G6PC (n = 1), AGL (n = 4), PYGL (n = 5), and PHKA2 (n = 1). AGL had two novel variants. The clinical manifestations were hepatomegaly (n = 8), doll-like facies (n = 3), wasting (n = 2), and stunting (n = 5). All patients showed hypoglycemia, transaminitis, and dyslipidemia. The mainstay of treatment was cornstarch supplementation and high-protein and low-lactose-fructose diet. After a median follow-up time of 9.59 years, height turned to normal for age in 3/5 patients and none had malnutrition. Liver enzymes, blood sugar, and lipid profiles improved in all. CONCLUSION Hepatomegaly, transaminitis, and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology. Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment, prognosis, and long-term care.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

Effect of GB1107, a novel galectin-3 inhibitor on pro-fibrotic signalling in the liver

Background and PurposeGalectin-3 (Gal-3) is a pro-fibrotic β-galactoside binding lectin highly expressed in fibrotic liver and implicated in hepatic fibrosis. GB1107 is a novel orally active Gal-3 small molecule inhibitor that has high affinity for Gal-3 >1000-fold selectively over other galectins. The aim of this study was to characterise GB1107 and galectin-3 in vitro and in vivo in the context of fibrosis signalling and liver disease. Experimental ApproachLiver fibrosis was induced by administration of CCl4 twice weekly by intraperitoneal injection in mice for 8 weeks. GB1107 was orally administered once daily (10 mg/kg) for the last 4 weeks of CCl4 treatment. Fibrosis was assessed by picrosirius red staining of FFPE sections. Liver enzymes, Gal-3 and downstream biomarkers were assessed in liver and plasma. Paired-end sequencing was performed on the NextSeq 2000 platform. Pathway enrichment analysis was performed to determine enrichment of differentially expressed genes (DEGs) within Reactome pathways and Gene Ontology (GO) terms. Key ResultsGB1107 significantly reduced plasma transaminases and liver Gal-3 and reduced liver fibrosis. RNAseq analysis of whole liver showed that 1,659 DEGs were identified with CCl4 treatment compared to control. Pathways enriched in up-regulated genes in the CCl4 group included those related to the extracellular matrix, collagen biosynthesis and assembly, cell cycle and the immune system. Comparing GB1107 treatment with CCl4 control 1147 DEGs were identified. GB1107 effectively reversed the majority of the CCl4 induced gene changes. Conclusions and ImplicationsGB1107 attenuated liver fibrosis and highlights Gal-3 as a therapeutic target for hepatic fibrosis.

Supplementation of lysophospholipids in calf starter: effects on growth performance, blood metabolites, health, and ruminal ammonia nitrogen concentration

The aim of the current study was to evaluate the effects of a commercial mixture of Lysophospholipids (LPL) in calf starter on performance, blood metabolites, antioxidant capacity, liver enzymes concentration, and health status of pre-weaning dairy calves. Forty-eight newborn female Holstein calves (37.5 ± 2.9kg of body weight) were randomly assigned to four treatments (12 replicates), which included the control (CON, without additive) and a commercial blend of LPL at 0.5, 1, and 1.5g/kg of starter feed. The body weight of the calves was measured using a digital scale on days 15, 30, 45, and d 63 of the experimental period to calculate the average daily gain (ADG). The individual starter intake and fecal score were measured daily. Blood samples were collected at 30 and 63 days, while fecal samples were collected for four consecutive days after weaning to measure nutrient digestibility. The treatments did not significantly afffect the total dry matter and starter intake. However, the supplementation of LPL resulted in an increase in the ADG and improved feed efficiency (FE, from1-63 d) compared to the CON group. The addition of LPL did not have any significant impact on the apparent digestibility of dry matter (DM), and organic matter (OM). Eether extract (EE) digestibility tended to increase with the addition of LPL. Calves that received starter feed containing 0.5g/kg of LPL had higher superoxide dismutase activity at 30 d of age compared to the intake.CON group. Additionally, the average fecal score significantly decreased in calves fed 0.5 and 1.5g/kg LPL compared with the CON group. These findings suggest that the inclusion of LPL at an average dose of 1g/kg of calf starter can improve the performance of pre-weaning Holstein dairy calves.

A likely pathogenic homozygous frameshift variant in BLOC1S6 associated with a rare form of congenital Hermansky-Pudlak syndrome 9

Hermansky-Pudlak syndrome (HPS) is a collection of autosomal recessive multisystemic disorders with at least 11 different types, categorized on the basis of involved genes. The disease is mostly characterized by tyrosinase-positive oculocutaneous albinism (OCA), platelet storage deficiency, absence of platelet dense bodies, and immune deficiency. Here we described a 2-month-old female infant with generalized hypotonia, recurrent infections, bilateral optic atrophy, nystagmus, cerebral atrophy, and elevated liver enzymes. Unlike her parents, she had chestnut colored hair, fair skin, and brown eyes. Parents had a consanguineous marriage, and their first child had died with similar symptoms at the age of 5 months. Whole exome sequencing (WES) was performed on DNA extracted from the patient's peripheral blood. Following the bioinformatics analysis, a likely pathogenic novel variant in the fifth exon of the BLOC1S6 gene (NM_001311255: c.506dupT: p. L169Ffs*33) was introduced by the Sadra Medical Genetic Laboratory. This variant was confirmed in the patient and segregated in both parents by Sanger sequencing.This report presented the first congenital case of HPS-9 worldwide that might have led to early neonatal death. Our current patient shows new considerable features related to the BLOC1S6 gene variant and HPS-9, which is a valuable source for future research, prediction, clinical management, genetic counseling, and prenatal diagnosing.

Diabetic foot ulcer healing potential of Tagetes erecta L. flower extract on successive administration in alloxan-induced diabetic rats via modulation of liver functions

Diabetes mellitus is a prevalent endocrine disorder characterized by inadequate insulin production by the pancreas or improper utilization of insulin by the body, which imposes severe health complications, including cardiovascular, kidney, and neurological disorders with a high potential of foot ulcers. Globally, diabetes is responsible for over 70 % of limb amputations. Alloxan was used to induce diabetes in rats while foot ulcers were induced by the excision method in diabetic rats. Diabetes was confirmed by measuring the parameters like blood glucose, body weight changes, urine excretion, and other biomarker levels after oral administration of Tagetes erecta L. flower extract (TEFE) at different doses. During the work, it was observed that TEFE demonstrated a dose-dependent effect on blood sugar level from 370.2 mg/dl to 113.00 mg/dl and healing of diabetic foot ulcers in a 13 days animal model (p < 0.01). There is significant decline in SGOT, SPGT and ALP levels when compared with diseased group animals. Decrease in wound size was observed when TEFE was administered to diabetic foot ulcer rats. These exciting results steered to enumerate the possible role of TEFE in Diabetes mellitus through a panel of mechanisms of action like inhibition of free radical generation, modulation of liver enzymes and metabolism of glucose etc. The above findings support the hypoglycaemic and diabetic foot ulcer healing potential of TEFE. Moreover, further investigation is required to completely understand the possible mechanism of TEFE.

Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver.

The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis. This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis. After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay. Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas. Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

Acute hepatitis in children: A wide clinical spectrum

Introduction: Acute hepatitis remains an important health problem in children. viral hepatitis particularly hepatitis A remains the most common cause. Nevertheless, other causes such as non A non B hepatitis and mixed infections like enteric fever are other causes particularly in developing countries like India. The spectrum of acute hepatitis is also varied with many atypical presentations in the form of fever along with icterus as presenting features. Use of lab parameters as prognostic markers for development of acute liver failure (ALF) needs further exploration as it can be used to identify patients who need better monitoring and may be the potential candidates for liver transplantation. In our study we have tried to find a possible association between liver enzyme values and number of children who develop ALF. Methods: Children between 1 and 15 years of age who presented with features of acute hepatitis were enrolled in the study after taking informed consent from their parents. Data was collected about their epidemiological and clinical characteristics in a predesigned study performa. Quantitative data were described as means and standard deviations and qualitative data were computed into frequency (No) and percentages (%). Chi-square (χ2) test was used to determine the statistical difference between the categorical variables, while means were compared using student’s t test. For all statistical analyses, p value &lt; 0.05 was adopted as level of significance. Results: We enrolled 68 patients of acute hepatitis. Most of them were males (78%) and majority were in 6 to 10 years age category. The most common clinical presentation was with abdominal pain followed by fever and icterus. Liver enzymes were raised to the tune of 10 to 20 times in the second week of illness. Serum bilirubin mean value was 5.3. Serum bilirubin values remained almost constant over 3 weeks period while liver enzymes showed a decline. 26% patients presented with ALF. Also, liver enzyme values in the second week showed a positive association with development of ALF with higher values associated with a higher chance of development of ALF. Conclusion: Hepatitis A was the most important cause of acute hepatitis in children and albeit early, a significant proportion of them develop features of ALF. Regular monitoring of liver enzymes can serve as a prognostic marker for development of ALF. It requires larger level studies to use liver enzymes as prognostic markers of ALF in paediatric patients.

Intestinal failure-associated liver disease model: a reduced phytosterol intravenous lipid emulsion prevents liver injury.

Long-term parenteral nutrition in children often results in intestinal failure-associated liver disease (IFALD). Phytosterols are plant steroids in vegetable oil-based intravenous lipid emulsions (ILEs) that are associated with IFALD. We investigated whether a phytosterol-depleted soybean oil ILE, compared to standard soybean oil ILE, prevented hepatotoxicity in a murine IFALD model. Eight-week-old male C57BL/6 J mice were provided a fat-free high carbohydrate liquid dietfor 19 days. Mice were intravenously administered ILEs as the sole fat source: Intralipid® (commercially available soybean oil ILE), Omegaven® (commercially available fish oil ILE), a low phytosterol soybean oil ILE (L-SOLE) or a high phytosterol soybean oil ILE (H-SOLE) with matched alpha tocopherol content. On days 6, 12, and 18 mice were administered escalating intraperitoneal doses of lipopolysaccharide. Compared to chow controls, mice that received Intralipid® demonstrated elevated plasma biomarkers of liver injury and histologic liver disease (hepatosteatosis, histologic inflammation, F4/80 staining). L-SOLE prevented both biochemical and histologic liver injury. Administration of H-SOLE also prevented biochemical liver injury, but not steatosis. The combination of phytosterol removal and alpha tocopherol supplementation may reduce the toxicity associated with parenteral use of soybean oil-based ILE. Low phytosterol soybean oil may be a valuable component in safer next generation ILEs. Half of children receiving long-term parenteral nutrition develop intestinal failure-associated liver disease (IFALD). Standard intravenous lipid emulsions (ILEs) in parenteral nutrition are vegetable oil based and high in phytosterols (plant steroids); no low phytosterol vegetable oil-based ILE is available. Phytosterols in ILEs are associated with IFALD. In this study, a new phytosterol-depleted soybean oil was utilized in a laboratory-generated ILE. Use of the phytosterol-depleted soybean oil ILE prevented liver injury in a murine model of IFALD. Phytosterol-depleted soybean oil may be utilized as a component of less toxic next-generation ILEs.

Red Rice DE 40 Alleviates High-fat Diet-induced Hyperlipemia by Lowering Lipid Profiles in Rats

Background Hyperlipidaemia is characterised by an abnormal increase in one or more lipids in plasma, and is a major contributor to obesity, coronary heart disease, myocardial infarction, and stroke if they are not treated promptly. Objectives In this study, we intended to discover the therapeutic actions of Red Rice DE 40 (RR DE 40) on high-fat diet (HFD)-induced rats. Materials and Methods The experimental rats were fed with HFD for 90 days to initiate the hyperlipidaemia and subsequently treated with 250 and 500 mg/kg of RR DE 40 from 60th to 90 days. The body weight of the rats was measured regularly. After the scarification, the blood, liver, and adipose tissue specimens were collected for biochemical assays. The liver and adipose tissues were weighed properly. The levels of haematological indices were counted using a haemocytometer. The levels of biochemical markers and liver marker enzymes were assessed using standard methods. The levels of lipid profiles were determined by standard methods. The excised liver and adipose tissues were analysed microscopically by histopathological analysis. Results RR DE 40 treatment effectively decreased the body weight gain in the HFD-induced rats. The liver and adipose tissue weight was also reduced by the RR DE 40 treatment. The changes in the haematological parameters such as RBC, WBC, Hb, monocytes, lymphocytes, and polymorphs were modulated by the RR DE 40 treatment on EG-induced rats. The levels of total protein, albumin, glucose, and urea and activities of SGOT and SGPT were substantially decreased by the RR DE 40 treatment. The RR DE 40 treatment also diminished the status of TC, TG, LDL, and VLDL in the HFD-treated rats. The findings of histopathological analysis also witnessed the therapeutic effects of RR DE 40. Conclusion The findings of this work highlighted that RR DE 40 is effective in HFD-induced hyperlipidaemia, probably due to its lipid-lowering potential. Hence, it may be used for the treatment of hyperlipidaemia-associated diseases.

Hepatotoxicological Evaluation of Parsonsia straminea (R.Br) F. Muel Stem Bark Crude Extract in Mice

Background: Toxicity is defined as the degree to which a substance can harm humans or animals. In reality, every entity that makes substances is undoubtedly labeled poisonous except it is quantified to make safety certain for therapeutic purposes. Herbal medicines are generally considered to be safe and efficacious among people of various ethnic backgrounds globally. The plant Parsonsia straminea has been traditionally claimed to be used in arthritis and seizures, although it is not widely explored. P. straminea a plant used medicinally cannot be said to be free from toxicity owing to fact on its use. Aim of the Study: The aim of the study is to assess the potential hepatotoxicity of P. straminea stem bark extract in mice Methodology: For the study, about thirty rodents (mice) were set into six groups with five (5) mice in each group. The study groups (GPs) include 1=0.2ml/kg of distilled water as control; 2 to 6=50,100,200,400 and 800 mg/kg of P. straminea extract. The harvested tissues were sent for histopathological examination. Results: This study has proven that the extract relatively impacted no significant toxicity on the liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB) aspartate aminotransferase (AST) and total protein (TP). Conclusion: The study findings have shown that the ethanolic stem bark of P. straminea possesses relatively no remarkable toxicity impact on the liver as revealed in the liver enzymes and the histology assessment.

Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats.

N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.

Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats

IntroductionWomen with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments.MethodsUsing timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments.ResultsHELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival.ConclusionHELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension.

Efficacy and safety of resmetirom for the treatment of nonalcoholic steatohepatitis: a GRADE assessed systematic review and meta-analysis.

There are no Food and Drug Administration (FDA)-approved treatment options for nonalcoholic steatohepatitis (NASH) which is a prevailing disease that leads to fibrosis, cirrhosis, or hepatocellular carcinoma. Hence, this systematic review and meta-analysis aims to determine the efficacy and safety of resmetirom, the first FDA-approved drug, for the treatment of NASH. A Grading of Recommendations, Assessment, Development, and Evaluation assessed systematic search of Cochrane Library, MEDLINE, Scopus, and Google Scholar database was conducted from inception till 31 March 2024. Meta-analyses were carried out in accordance with the PRISMA statement. Heterogeneity was determined to be significant if found above 50%. This meta-analysis encompasses three randomized clinical trials, including a total of 2231 patients. The findings show resmetirom's significant efficacy in several key outcomes, including improvement in fibrosis risk ratios, 1.67 [95% confidence intervals (CI), 1.26-2.20], reductions in liver fat content (95% CI, -39.58 to -23.5), and enhanced liver fibrosis score (95% CI, -0.37 to -0.13) along with improved levels of liver enzymes. Resmetirom was found to be associated with nausea and diarrhea. This is the first systematic review and meta-analysis to determine the safety and efficacy of resmetirom which showed significant positive results in fibrosis improvement, liver fat content, lipid profiles, and liver enzymes in comparison to placebo. Moreover, moderate side effects, such as diarrhea and nausea, were seen in few patients indicating a satisfactory safety profile.

Evaluation of the Effects of Petrochemical to Liver Enzymes of Fuel Attendants in Oluyole Area, Ibadan, Nigeria

Evaluation of the Effects of Petrochemical to Liver Enzymes of Fuel Attendants in Oluyole Area, Ibadan, Nigeria

Atypical Presentation of Subcapsular Liver Hematoma With a Delayed Onset of Hemolysis, Elevated Liver Enzymes, Low Platelet Count (HELLP) Syndrome

Atypical Presentation of Subcapsular Liver Hematoma With a Delayed Onset of Hemolysis, Elevated Liver Enzymes, Low Platelet Count (HELLP) Syndrome

Effects of 3-month liraglutide treatment on oxidative stress and inflammation in type 2 diabetes patients with different urinary albumin-to-creatinine ratio categories

This study evaluates the effects of liraglutide on albuminuria, oxidative stress, and inflammation in type 2 diabetes (T2D) patients with different urinary albumin-to-creatinine ratio (UACR) categories. We enrolled 107 patients with T2D who were initiating liraglutide for glycemic control. Patients were categorized into 3 groups: group I (UACR &lt; 30 mg/g); group II (30 mg/g ≤ UACR ≤ 300 mg/g); group III (UACR &gt; 300 mg/g). We observed the changes in body mass index, fasting plasma glucose, glycated hemoglobin, lipid profile, serum liver enzymes, creatinine, uric acid, cystatin C, UACR, as well as oxidative stress and inflammation biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase before and after 3 months of liraglutide treatment. After 3-month liraglutide treatment, fasting plasma glucose, glycated hemoglobin, and body mass index significantly decreased in all 3 groups regardless of the baseline UACR (all P &lt; .05). UACR significantly decreased in groups II (P = .005) and III (P = .001). Patients with higher UACR at baseline showed significantly greater albuminuria reduction (P &lt; .001). Compared with baseline, TNF-α, IL-6, MCP-1, and MDA were remarkably decreased, while SOD and glutathione peroxidase were significantly increased in all 3 groups (P &lt; .05). UACR at baseline showed a positive correlation with TNF-α, IL-6, and MDA, and a negative correlation with SOD at baseline. The change in UACR was negatively correlated with UACR, TNF-α, and MDA at baseline, while it was positively correlated with SOD at baseline, and also positively correlated with the change in MCP-1. Liraglutide ameliorated albuminuria in T2D patients with microalbuminuria and macroalbuminuria. The renoprotective effect of liraglutide was associated with the alleviation of oxidative stress and inflammation. These findings may provide new therapeutic strategies for patients with diabetic kidney disease.

Hepatokine leukocyte cell-derived chemotaxin 2 as a biomarker of insulin resistance, liver enzymes, and metabolic dysfunction-associated steatotic liver disease in the general population.

Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-associated hepatokine that causes skeletal muscle insulin resistance. Since LECT2 is up-regulated by the inactivation of the energy sensor AMPK in the liver, we hypothesized that LECT2 has potential as a biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we investigated whether circulating LECT2 levels are associated with insulin sensitivity, liver enzymes, and MASLD. This cross-sectional study included 138 Japanese individuals. Plasma LECT2 levels were measured using fasting blood samples. B-mode ultrasonography was used to assess hepatic steatosis. The mean age and body mass index (BMI) of participants were 63.5 ± 10.2 years and 23.0 ± 3.1 kg/m2, respectively. Higher LECT2 levels positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) values and negatively correlated with the quantitative insulin sensitivity check index (QUICKI) among all participants (HOMA-IR; non-standardized β (B) = 6.38, P < 0.01: QUICKI; B = -161, P < 0.01). These correlations were stronger in the low BMI group (HOMA-IR; B = 13.85, P < 0.01: QUICKI; B = -180, P < 0.01). LECT2 levels also positively correlated with gamma-glutamyl transferase levels (B = 0.01, P = 0.01) and alanine aminotransferase levels (B = 0.33, P = 0.02). Higher LECT2 levels correlated with the prevalence of MASLD (odds ratio = 1.14, P = 0.02). The present results suggest the potential of plasma LECT2 levels as a biomarker for insulin resistance in individuals who are not overweight and the prevalence of MASLD in the general population.

The impact of overseas assignments on metabolic factors: Panasonic cohort study 23.

This study aimed to assess the effects of overseas assignments on the metabolic factors associated with lifestyle disease including body mass index, blood pressure, plasma glucose, lipid profiles, liver enzyme, and uric acid in Japanese individuals. A retrospective cohort study was conducted using annual health examination data from employees of the Panasonic Corporation in Japan. We evaluated the differences in the changes in metabolic factors associated with lifestyle disease during the observation periods between the overseas and non-overseas assignment groups. Propensity score matching was performed to match the characteristics of the two groups. In subgroup analysis, the impact of family accompaniment and the destination on metabolic factors associated with lifestyle disease were also evaluated. The median ages of the overseas (n = 899) and non-overseas assignment groups (n = 899) were 46 (41-50) and 46 (41-50) years. The average overseas assignment duration was 4.1 ± 1.7 years. Overall, 65.4% of individuals were assigned overseas alone in the overseas assignment group. No significant differences were observed in the changes in metabolic factors associated with lifestyle disease between the overseas and non-overseas assignment groups. In subgroup analyses, the family accompaniment and the destination did not affect changes in any of metabolic factors associated with lifestyle disease during the overseas assignment. In conclusion, no significant difference was observed in metabolic factors associated with lifestyle disease between the overseas and non-overseas assignment groups in Japanese employees.