Liver Enzyme Levels Research Articles

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Protective effect of magnetic water against AlCl3-induced hepatotoxicity in rats

This study aimed to examine whether or not aluminum chloride (AlCl3)-induced hepatotoxicity might be mitigated using magnetic water (MW) in rats. This study involved 28 adult male rats randomly assigned into the following 4 groups (7 rats/group): normal control (Cnt), MW, AlCl3, and Al Cl3 + MW. The Cnt group orally received normal saline, the MW group drank MW ad libitum for 2 months, and the AlCl3 and AlCl3 + MW groups were orally administered AlCl3 (40 mg/kg b.w.) alone or in combination with MW for 2 months, respectively. MW reduced AlCl3 toxicity as proved at functional, molecular, and structural levels. Functionally, MW reduced serum levels of liver enzymes (ALT, AST, ALP, GGT), while increased total proteins, and albumin. MW also restored redox balance in the liver (lower MDA levels, higher activities of CAT and SOD enzymes, and upregulated expression of NrF2, HO-1, and GST genes. Molecularly, MW downregulated hepatic expression of the epigenetic (HDAC3), inflammatory (IL1β, TNFα, NFκβ), and endoplasmic reticulum stress (XBP1, BIP, CHOP) genes. Structurally, MW enhanced liver histology. With these results, we could conclude that MW has the potential to ameliorate the hepatotoxic effects of AlCl3 through targeting oxidative stress, inflammation, epigenesis, and endoplasmic reticulum stress.

Silybin Meglumine Mitigates CCl4-Induced Liver Fibrosis and Bile Acid Metabolism Alterations.

Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Silybin meglumine (SLB-M) is widely used in treating various liver diseases including liver fibrosis. However, research on its effects on bile acid (BA) metabolism is limited. This study investigated the therapeutic effects of SLB-M on liver fibrosis and BA metabolism in a CCl4-induced murine model. A murine liver fibrosis model was induced by CCl4. Fibrosis was evaluated using HE, picrosirius red, and Masson's trichrome staining. Liver function was assessed by serum and hepatic biochemical markers. Bile acid (BA) metabolism was analyzed using LC-MS/MS. Bioinformatics analyses, including PPI network, GO, and KEGG pathway analyses, were employed to explore molecular mechanisms. Gene expression alterations in liver tissue were examined via qRT-PCR. SLB-M treatment resulted in significant histological improvements in liver tissue, reducing collagen deposition and restoring liver architecture. Biochemically, SLB-M not only normalized serum liver enzyme levels (ALT, AST, TBA, and GGT) but also mitigated disruptions in both systemic and hepatic BA metabolism by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4-induced murine model. Notably, SLB-M efficiently improved the imbalance of BA homeostasis in liver caused by CCl4 via activating Farnesoid X receptor. These findings underscore SLB-M decreased inflammatory response, reconstructed BA homeostasis possibly by regulating key pathways, and gene expressions in BA metabolism.

A Scoping Review on Hepatoprotective Mechanism of Herbal Preparations through Gut Microbiota Modulation.

Liver diseases cause millions of deaths globally. Current treatments are often limited in effectiveness and availability, driving the search for alternatives. Herbal preparations offer potential hepatoprotective properties. Disrupted gut microbiota is linked to liver disorders. This scoping review aims to explore the effects of herbal preparations on hepatoprotective mechanisms, particularly in the context of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatic steatosis, with a focus on gut microbiota modulation. A systematic search was performed using predetermined keywords in four electronic databases (PubMed, Scopus, EMBASE, and Web of Science). A total of 55 studies were included for descriptive analysis, covering study characteristics such as disease model, dietary model, animal model, intervention details, comparators, and study outcomes. The findings of this review suggest that the hepatoprotective effects of herbal preparations are closely related to their interactions with the gut microbiota. The hepatoprotective mechanisms of herbal preparations are shown through their effects on the gut microbiota composition, intestinal barrier, and microbial metabolites, which resulted in decreased serum levels of liver enzymes and lipids, improved liver pathology, inhibition of hepatic fatty acid accumulation, suppression of inflammation and oxidative stress, reduced insulin resistance, and altered bile acid metabolism.

Comparison of Characteristics and Outcomes of Hepatitis B and Hepatitis C Patients in the Fars Hepatitis Registry

Background: Hepatitis, which refers to liver inflammation, can have various causes, with viral hepatitis being the most common. Objectives: This study aimed to compare demographic and laboratory variables, risk factors, and outcomes between Hepatitis B (HBV) and Hepatitis C (HCV) patients in the Fars hepatitis registry. Methods: In this cross-sectional study, a total of 6,690 eligible patients, consisting of 3,840 (57.4%) with HBV and 2,820 (42.6%) with HCV, were assessed from the database covering the period from 1995 to 2023. Comparisons between HBV and HCV were made using the Chi-square test, Fisher's exact test, or independent sample t-test with SPSS software. Results: The average age of the patients was 52.56 years (standard deviation: 13.24). Significant differences were found between HBV and HCV patients regarding sex, marital status, education level, family history of HBV and HCV, smoking status, drug use, and body mass index (P < 0.001 for all). Hepatitis B patients had a higher prevalence of dental procedures (P < 0.001) and uncertain sexual contacts (P = 0.009), while blood transfusion, intravenous drug use, major thalassemia (P < 0.001 for all), tattoos (P = 0.004), and hemodialysis (P = 0.001) were more common in HCV patients. Hepatitis C patients showed higher levels of liver enzymes (P < 0.001) and total bilirubin (P = 0.002) but lower levels of albumin (P < 0.001) and prothrombin time (P = 0.034) compared to HBV patients. Cirrhosis was also more common in HCV patients (P < 0.001). Conclusions: Our findings highlight different patterns of demographic factors, risk factors, and outcomes between HBV and HCV patients, which could influence their prevention and management strategies.

A Case of Tick-borne Disease with Yezo Virus and Borrelia miyamotoi Coinfection.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

Selected Blood Biochemical Parameters after Right and Left Nephrectomy in Clinical Practice

Introduction. Radical nephrectomy is considered as a common operation associated with significant changes in the topography of the upper abdominal cavity which appear in the postoperative period. Analysis of the literature fails to provide sufficient information about functional changes in the parenchymatous abdominal organs that occur after nephrectomy. Aim. To investigate a number of liver and pancreatic enzymes in the blood of patients at the pre­ and post­ operative stages of the radical nephrectomy. Materials and methods. The study involved a retrospective analysis of medical records of 111 patients after radical nephrectomy. The patients underwent biochemical examination at the pre­operative stage, on day 1, and day 7 after the operation: ALT, AST, amylase, diastase. The examination was performed by means of biochemistry analyzers Bio Systems BA 400 and Beckman Coulter AU 480. Statistical data processing was carried out using Statistica 10.0. Results. The analysis of the obtained materials shows that the level of liver and pancreatic enzymes increases after radical nephrectomy. A side of the operation was revealed significant: left­sided nephrectomy leads to an increase in the level of blood amylase and diastase, right­sided nephrectomy results in an increase in the level of ALT and AST. No dependence on the sex of patients was determined. No increase in the level of the studied enzymes was found in a number of patients in the postoperative period; however, almost half of patients were detected with a significant, 1.5–2 times and higher, increase in the level of enzymes, thus requiring special control and correction. The maximum level of ALT reached 245 U/L (norm 0–35 U/L), the maximum level of AST comprised 184 IU/L (norm 0–35 IU/L). Discussion. The obtained results indicate the interrelation of functional disorders of the liver and pancreas and changes in their topography after radical nephrectomy. Conclusion. Radical nephrectomy is associated with significant functional disorders of the liver and pancreas depending on the side of the operation: the level of blood amylase and diastase increases after left nephrectomy, the level of ALT and AST grows after right nephrectomy. The level of enzymes exceeds the norm by 1.5–2 times in almost half of patients.

The Impact of Labor Oxytocin Use on Newborn Liver Enzymes.

Oxytocin is commonly used during labor and delivery for induction of labor and prevention of postpartum hemorrhage. While previous studies have explored the effects of labor oxytocin use on maternal and neonatal outcomes, there is a paucity of research on its impact on newborn liver enzyme function. This study aimed to assess the effects of labor oxytocin use on liver enzyme function in newborns. A case-control study was conducted. The case group consisted of 70 newborns whose mothers received oxytocin during labor, while the control group consisted of 70 newborns whose mothers did not receive oxytocin. Complete blood count (CBC), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total and indirect bilirubin levels were measured in all newborns on the second day of life. The levels of AST and total and indirect bilirubin were found to be higher in the case group than in the control group (51 vs. 42, 7.8 vs. 4.6, and 7.4 vs. 4, respectively; p < 0.005). The levels of CPK and LDH were also higher in the case group (p < 0.005). However, the difference in ALT levels was not significant between the study groups. The observed increase in liver enzymes in this study can indicate the effect of maternal oxytocin on the newborn's liver function. While the changes in liver enzyme levels due to oxytocin use were not found to be high enough to cause liver damage, the increase in CPK and LDH levels could potentially elevate bilirubin levels due to hemolysis. Further research is needed to confirm these findings and explore the underlying mechanisms.

Lipid-lowering and antioxidant properties of probiotic Bifidobacterium animalis MSMC83 in rats on a high-fat diet.

Hyperlipidaemia, the abnormally high concentration of lipids such as cholesterol in the body, has a series of deleterious effects on health that are least in part are due to increased inflammation and oxidative stress. Probiotics are living microorganisms that possess the efficacy to improve health. Among the many effects that have been ascribed to probiotics is the potential to lower the body lipid content. Here, we used a rat model of induced hyperlipidaemia to assess the lipid-lowering and antioxidant properties of the probiotic strain Bifidobacterium animalis MSMC83 as well as its impact on intestinal barrier immunity and the intestinal microbiota. Oral probiotic intake led to a reduction of body weight, fasting blood glucose, and lipid levels, and increased expression of cholesterol-7α-hydroxylase and antioxidant enzymes. Additionally, B. animalis MSMC83 decreased the levels of liver enzymes and pro-inflammatory cytokines, leading to reduced hepatic steatosis. Furthermore, it re-established intestinal barrier integrity as shown by restoration of the tight junction protein zonula occludens-1 amount and reduced pathogen-induced inflammation in the intestinal epithelium as shown by readjusted expression of toll-like receptors (TLRs). Moreover B. animalis MSMC83 contributed to the maintenance of a balanced, diverse microbiome. Thus, our results indicate that B. animalis MSMC83 alleviates risk factors associated with hyperlipidaemia, suggesting its use as a probiotic to counter the effects associated with unhealthy diets.

Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies.

Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses. Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses. In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes. Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.

The Effectiveness of Letrozole Alone or in Combination with Methotrexate in the Management of Ectopic Pregnancy, A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the effect of letrozole alone or in combination with Methotrexate on the management of ectopic pregnancy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied for reporting. The EMBASE, PubMed, Scopus, and Web of Science databases were searched for relevant studies focused on women diagnosed with ectopic pregnancy and managed non-surgically with letrozole alone or in combination with methotrexate (MTX) until April 2024. The success rate, laboratory findings, and complications were analyzed and reported. Meta-analysis was done using RevMan 5.4.1 software. Out of 129 unique studies obtained, 7 of them were found eligible for final review; of which, 3 were nonrandomized prospective cohort studies, 2 were randomized clinical trials, and 2 study were case studies. In 5 studies letrozole was used as monotherapy. While in another study letrozole was used with MTX. The meta-analysis showed a significantly lower level of β-HCG in the letrozole group compared to MTX, 7days after initiation of treatment (Fixed effect model, MD = -92.22, 95%CI: [-159.39, -25.04], P = 0.007, I2 = 0%). There was no significant difference in the level of anti-mullerian hormone (AMH) between groups (Fixed effect model, MD = 0.18, 95%CI: [-0.09, 0.45], P = 0.20, I2 = 0%). Success rate, platelet count, and level of liver enzymes seemed to be better or similar among patients receiving Letrozole compared to patients receiving Methotrexate. Letrozole exhibits potential as a therapeutic option for ectopic pregnancies; however, further randomized clinical trials are necessary to establish strong evidence.

Efficacy and safety of Dapagliflozin and Glimepiride in combination with Metformin: Randomized clinical trial

Objective: To identify the effective treatment option between dapagliflozin-metformin and glimepiride-metformin combination in patients with type 2 diabetes who were inadequately controlled with metformin monotherapy. Study design and setting: The present study is randomized, conducted for 12 weeks at the National Medical center, Karachi, Pakistan. Methodology: The patients were divided into 2 treatment groups; group A was given dapagliflozin-metformin combination, while group B was given glimepiride-metformin combination. The efficacy endpoint of groups was estimated by hemoglobin A1c and fasting blood glucose levels at 0-, 6- and 12-week. While, safety endpoints were identified by analyzing liver function tests, lipid profile tests, renal function test, and urine analysis. The significant difference of data was analyzed by using statistical package of social sciences (SPSS) version 25. The parametric t-test and paired t-test were performed and considered p-value = 0.05 as statistical significant. Results: Baseline demographics, clinical features of diabetes, levels of liver enzymes, liver function test, renal function test, lipid profile, and urinalysis of randomized patients were similar in both treatment groups by showing p = 0.05. Followed by the initiation of the respective treatment, the baseline change of mean FBG and hemoglobin A1c levels with dapagliflozinmetformin combination was shown significantly reduce more compared to glimepiride-metformin combination (p = 0.05). Conclusion: Dapagliflozin-metformin combination therapy was superior and well-tolerated to regulate glycemic control as compare to glimepiride-metformin combination

Serum metabonomics reveal the effectiveness of human placental mesenchymal stem cell therapy for primary sclerosing cholangitis.

The metabolic patterns of human placental-derived mesenchymal stem cell (hP-MSC) treatment for primary sclerosing cholangitis (PSC) remain unclear, and therapeutic effects significantly vary due to individual differences. Therefore, it is crucial to investigate the serological response to hP-MSC transplantation through small molecular metabolites and identify easily detectable markers for efficacy evaluation. Using Mdr2-/- mice as a PSC model and Mdr2+/+ mice as controls, the efficacy of hP-MSC treatment was assessed based on liver pathology, liver enzymes, and inflammatory factors. Serum samples were collected for 12C-/13C-dansylation and DmPA labeling LC-MS analysis to investigate changes in metabolic pathways after hP-MSC treatment. Key metabolites and regulatory enzymes were validated by qRT-PCR and Western blotting. Potential biomarkers of hP-MSC efficacy were identified through correlation analysis and machine learning. Collectively, the results of the liver histology, serum liver enzyme levels, and inflammatory factors supported the therapeutic efficacy of hP-MSC treatment. Based on significant differences, 41 differentially expressed metabolites were initially identified; these were enriched in bile acid, lipid, and hydroxyproline metabolism. After treatment, bile acid transport was accelerated, whereas bile acid production was reduced; unsaturated fatty acid synthesis was upregulated overall, with increased FADS2 and elongase expression and enhanced fatty acid β-oxidation; hepatic proline 4-hydroxylase expression was decreased, leading to reduced hydroxyproline production. Correlation analysis of liver enzymes and metabolites, combined with time trends, identified eight potential biomarkers: 2-aminomuconate semialdehyde, L-1-pyrroline-3-hydroxy-5-carboxylic acid, L-isoglutamine, and maleamic acid were more abundant in model mice but decreased after hP-MSC treatment. Conversely, 15-methylpalmitic, eicosenoic, nonadecanoic, and octadecanoic acids were less abundant in model mice but increased after hP-MSC treatment. This study revealed metabolic regulatory changes in PSC model mice after hP-MSC treatment and identified eight promising biomarkers, providing preclinical evidence to support therapeutic applications of hP-MSC.

5150 When Few Options Exist: Graves’ Disease Treated with Potassium Iodide and Levothyroxine Block-and-Replace Therapy

Abstract Disclosure: O. Magvanjav: None. S.K. Majumdar: None. Background: In the US, methimazole and propylthiouracil are effective first-line agents for the treatment of Graves’ disease. However, side effects including liver dysfunction may limit their use. In such instances, alternative non-conventional agents such as potassium iodide (KI) may be considered. Here, we present a case of a patient with Graves’ disease successfully treated with KI, drawing on the example of similar treatment experiences in Japan. Clinical case: Our patient is a 29-year-old woman who presented with a 3-week history of palpitations accompanied by fatigue, heat intolerance, itchiness, insomnia, and unintentional weight loss. Exam was notable for tachycardia (135 bmp), elevated blood pressure (BP) (150/81 mmHg), normal temperature, slight thyromegaly, brisk reflexes, mild anxiousness, and tremulousness. She was found to have a TSH of 0.007 mIU/ml (normal: 0.270-4.200 mIU/ml), elevated free T4 of 5.19 ng/dl (normal: 0.80-1.70 ng/dL), total T3 of 330 ng/dl (normal: 72.0-153.0 ng/dl), total T4 of 12.1 ug/dl (normal: 4.5-11.7 ug/dl), and positive antibodies (TSI 443%; TRAB 5.42 IU/L). A thyroid ultrasound showed diffuse hyperemia and a 1.4 cm right lobe TR3 nodule. She had a normal baseline neutrophil count with mild eosinophilia; a baseline hepatic function panel was not obtained. She was started on methimazole 20 mg daily and metoprolol XL 50 mg daily for symptom control. One week into treatment, a hepatic function panel showed elevated liver enzyme levels: AST 70 U/L (normal: 10-35 U/L) and ALT 223 U/L (normal: 10-35 U/L); previous values from 2 years prior were normal. Repeat levels a few days later showed increasing liver enzyme levels (AST 83 U/L; ALT 268 U/L) despite decreasing thyroid hormone levels. Methimazole was stopped, and she was then seen by a gastroenterologist, who concurred with the possibility of an adverse drug reaction to methimazole. She declined definitive therapy with surgery or radioactive iodine therapy and wanted to pursue alternative and less invasive options. Drawing on a previous successful experience from Japan, we initiated her on KI (50 mg twice daily), which resulted in normalization of her thyroid hormones within two weeks of initiation. She subsequently developed hypothyroidism 2 months later, at which point we initiated block-and-replace therapy with the addition of 50 mcg of levothyroxine. Her liver enzymes normalized with normalization of thyroid hormones. Conclusions: We present a patient with symptomatic Graves’ disease who was successfully treated with KI in the setting of limited treatment options, specifically an adverse reaction to methimazole (transaminitis), and who declined both surgery and radioactive iodine. This case demonstrates that KI may be useful in Graves’ disease as either a bridge to more definitive therapy when thioamides are not tolerated, or perhaps as a treatment option for those most likely to go into remission. Presentation: 6/1/2024

7490 Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 inhibitors; Switch Study in Real-World Setting

Abstract Disclosure: H. Choe: None. M. Kwak: None. J. Lee: None. Y. Choi: None. E. Hong: None. Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) represent two distinct pharmacological pathways in the management of type 2 diabetes, both aiming to improve glycemic control without risk of hypoglycemia. Metabolic implications and glycemic control associated with the interchange between SGLT2i and DPP-4i are scarce. This study aimed to evaluate the effect of switching between SGLT2i and DPP4i on various clinical parameters in Korean patients with type 2 diabetes. Methods: We conducted a retrospective cohort study at Hallym University Dongtan Sacred Heart Hospital, using clinical data warehouse. Baseline measurements and follow-up data at 3 months were collected for parameters including hemoglobin A1c (HbA1c), blood pressure, lipid profile, liver enzymes, renal function, and other metabolic markers. Results: Between 2015 and 2023, 104 participants switched from SGLT2 inhibitors to DPP4 inhibitors, while 321 switched in the opposite direction. Initially, those who switched from SGLT2 inhibitors to DPP4 inhibitors presented with lower baseline HbA1c levels (7.22 ± 0.73% versus 7.42 ± 0.76%, P = 0.017) and higher estimated glomerular filtration rates (eGFR) (95.2 ± 23.1 versus 85.9 ± 23.7 mL/min/1.73m², P = 0.001) compared to those who switched from DPP4 inhibitors to SGLT2 inhibitors. At three months of follow-up, the SGLT2 inhibitors to DPP4 inhibitors group exhibited a more significant reduction in HbA1c (adjusted β 0.22, 95% CI 0.03 to 0.40, P = 0.023), especially in patients with reduced eGFR (&amp;lt;60 mL/min/1.73 m²) (β 1.2, 95% CI 0.30 to 2.11, P = 0.013; P for interaction = 0.005). On the other hand, the DPP4 inhibitors to SGLT2 inhibitors group showed a greater decrease in fasting glucose levels (β -9.73, 95% CI -17.6 to -1.86, P = 0.016), along with more pronounced reductions in liver enzymes AST (β -4.15, 95% CI -6.49 to -1.81, P &amp;lt; 0.001) and ALT (β -6.42, 95% CI -9.58 to -3.27, P &amp;lt; 0.001), and a significant increase in hematocrit (β 3.31, 95% CI 2.36 to 4.26, P &amp;lt; 0.001) compared to the initial group. Conclusions: The study concludes that in Korean patients with type 2 diabetes, switching from SGLT2 inhibitors to DPP4 inhibitors is associated with a greater reduction in HbA1c, particularly in those with reduced renal function. Conversely, switching from DPP4 inhibitors to SGLT2 inhibitors results in more substantial improvements in fasting glucose and liver enzyme levels, suggesting differential benefits depending on the direction of the medication switch. Presentation: 6/3/2024

Salidroside may target PPARα to exert preventive and therapeutic activities on NASH.

Salidroside (SDS), a phenylpropanoid glycoside, is an antioxidant component isolated from the traditional Chinese medicine Rhodiola rosea and has multifunctional bioactivities, particularly possessing potent hepatoprotective function. Non-alcoholic steatohepatitis (NASH) is one of the most prevalent chronic liver diseases worldwide, but it still lacks efficient drugs. This study aimed to assess the preventive and therapeutic effects of SDS on NASH and its underlying mechanisms in a mouse model subjected to a methionine- and choline-deficient (MCD) diet. C57BL/6J mice were fed an MCD diet to induce NASH. During or after the formation of the MCD-induced NASH model, SDS (24mg/kg/day) was supplied as a form of diet for 4weeks. The histopathological changes were evaluated by H&E staining. Oil Red O staining and Sirius Red staining were used to quantitatively determine the lipid accumulation and collagen fibers in the liver. Serum lipid and liver enzyme levels were measured. The morphology of autophagic vesicles and autophagosomes was observed by transmission electron microscopy (TEM), and qRT-PCR and Western blotting were used to detect autophagy-related factor levels. Immunohistochemistry and TUNEL staining were used to evaluate the apoptosis of liver tissues. Flow cytometry was used to detect the composition of immune cells. ELISA was used to evaluate the expression of serum inflammatory factors. Transcript-proteome sequencing, molecular docking, qRT-PCR, and Western blotting were performed to explore the mechanism and target of SDS in NASH. The oral administration of SDS demonstrated comprehensive efficacy in NASH. SDS showed both promising preventive and therapeutic effects on NASH in vivo. SDS could upregulate autophagy, downregulate apoptosis, rebalance immunity, and alleviate inflammation to exert anti-NASH properties. Finally, the results of transcript-proteome sequencing, molecular docking evaluation, and experimental validation showed that SDS might exert its multiple effects through targeting PPARα. Our findings revealed that SDS could regulate liver autophagy and apoptosis, regulating both innate immunity and adaptive immunity and alleviating inflammation in NASH prevention and therapy via the PPAR pathway, suggesting that SDS could be a potential anti-NASH drug in the future.

Investigating the effect of adding silymarin to the standard treatment of naloxone in methadone intoxication; a double-blind clinical trial

Introduction: In cases of methadone intoxication, the drug is mainly processed by the liver, however, its elimination through the kidneys is also crucial. On the other hand, naloxone therapy is a gold standard treatment for opioid intoxication, the addition of other drugs can improve its benefits and reduce side effects. Objectives: This study aimed to assess the effectiveness of adding silymarin to the standard treatment of naloxone in patients with methadone intoxication, to improve patient outcomes and reduce the risk of complications associated with alone naloxone therapy. Patients and Methods: This clinical trial study aimed to investigate the efficacy of silymarin in combination with standard treatment for methadone intoxication patients. The study employed a control group, which received standard treatment with naloxone, and an intervention group, which received both naloxone and silymarin. Liver functional tests (LFTs), kidney functional tests, malondialdehyde (MDA), and ferric-reducing ability of plasma (FRAP) were measured at admission and post-intervention times to compare the outcomes between the two groups. Statistical analyses, including chi-square, independent and paired t tests, Wilcoxon, and Mann-Whitney tests were conducted to identify significant differences between the groups. Results: Results indicated that 32 and 33 patients were included in the naloxone and naloxone + silymarin groups, respectively. The results showed that the changes in kidney functional tests such as blood urea nitrogen (BUN) and creatinine (Cr), MDA, and FRAP were not statistically significant between the two groups. However, the changes in LFTs, including, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), were statistically significant. Notably, the LFT changes were more pronounced in the group receiving both naloxone and silymarin, indicating a greater reduction in liver enzymes in this combined treatment group. Conclusion: The addition of silymarin to standard naloxone treatment for methadone intoxication patients could improve liver function, as the combined therapy showed a more pronounced reduction in liver enzyme levels compared to standard treatment alone; however, this combination treatment could not change the kidney function and oxidative stress markers. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20210216050377N1; ethical code from Shahrekord University of Medical Sciences; IR.SKUMS.REC.1400.048). This study was also registered in Research Registry website with Unique Identifying Number (UIN) of researchregistry10395.

Are Systemic Inflammation Markers Reliable for Diagnosing Intrahepatic Cholestasis of Pregnancy? A Retrospective Cohort Study.

This study aims to evaluate the effectiveness of inflammation indexes (systemic immune-inflammation index [SII], systemic inflammation response index [SIRI], pan-immune inflammation value [PIV], and neutrophil-to-lymphocyte ratio [NLR]) in the diagnosis of intrahepatic cholestasis of pregnancy (ICP). A retrospective study was conducted, reviewing medical records of patients diagnosed with ICP who delivered between October 1, 2022, and May 31, 2023, at the Perinatology clinic of Etlik City Hospital, Ankara. A control group of healthy pregnant women with uncomplicated pregnancies was also included. Demographic data, clinical characteristics, and laboratory results, including systemic inflammation indices and liver enzyme levels, were collected and analyzed. A total of 242 participants were included, with 121 ICP patients and 121 controls. White blood cell count, neutrophil count, and monocyte count showed significant differences between the two groups (p = 0.011, p = 0.004, and p = 0.039, respectively). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly elevated in the ICP group (p < 0.001 for both). SII and NLR were higher in the ICP group compared to controls (p = 0.032 and p = 0.010, respectively). Receiver operating characteristic (ROC) analysis revealed moderate predictive values for SII (area under the curve [AUC] = 0.581, p = 0.030) and NLR (AUC = 0.598, p = 0.009), with no significant difference in their predictive power (p = 0.502). Systemic inflammation indices such as SII and NLR offer a cost-effective and rapid means of diagnosing ICP, potentially complementing or surpassing traditional biomarkers like bile acid levels and liver function tests (LFTs). These indices can be easily integrated into routine clinical practice, providing timely intervention to improve maternal and fetal outcomes. Further research is warranted to confirm these findings and establish standardized protocols for their use in ICP management.

Long-Term Survival in Canine Hepatosplenic T-Cell Lymphoma Treated with Toceranib Phosphate Following Splenectomy: A Case of Atypical Lymphoma

Toceranib phosphate (toceranib) is approved for canine mast cell tumor treatment. However, no long-term response to toceranib in canine HSTCL has been reported. Here, we describe a case of a 10-year-old castrated mixed-breed dog that presented with a 3-month history of weight loss, polydipsia, and polyuria. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and splenomegaly with multiple diffuse splenic hypoechoic nodules. On day 21, a cholecystectomy was performed to remove the obstruction, followed by a liver biopsy and splenectomy. Cytology of the spleen and liver showed many small lymphocytes with intracytoplasmic granules (sGLs). Splenic and hepatic infiltration of neoplastic CD3/granzyme B-positive small cells and lymphocytic cholecystitis with granzyme B-negative small cells were noted. T-cell receptor gene clonal rearrangements were observed in the liver tissues. The dog was diagnosed with a hepatosplenic T-cell lymphoma (HSTCL) of sGLs concurrent with lymphocytic cholecystitis. The icterus resolved after surgery, but there was progressive elevation of liver enzyme levels. Toceranib was administered from day 39, resulting in decreased liver enzyme levels, and the dog remained in good condition. The dog stayed in remission after toceranib administration and survived for 460 days. Toceranib should be considered an effective treatment option for canine HSTCL.

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.