Changes In Liver Enzymes Research Articles

Hemangiossarcoma hepático em cadela da raça Dobermann

In this work, a case is reported of a young Doberman dog, with a history of ingesting cica palm (Cycas revoluta), in the first months of life, she presented changes in liver enzymes. The patient was diagnosed with primary hepatic hemangiosarcoma, which is a malignant neoplasm of epithelial cells, and is highly metastatic in its visceral form. The diagnosis was made through exploratory laparotomy and histopathological results. In addition, complementary hematological and imaging tests were performed for follow-up. Eight chemotherapy sessions with doxorubicin were performed. Due to the aggressiveness of this neoplasm, the prognosis is reserved to unfavorable. During treatment, the patient developed dilated cardiomyopathy, progressing to heart failure, which was the cause of death. The objective of this report is to present a case of primary hepatic hemangiosarcoma, raising the possible cause related to the carcinogenic agent responsible for its development.

Impact of trastuzumab emtansine (T-DM1) on spleen volume in patients with HER2-positive metastatic breast cancer.

Trastuzumab emtansine (T-DM1) is a novel therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, combining the targeted action of trastuzumab with the cytotoxic effects of emtansine. Although T-DM1 has demonstrated greater efficacy and safety compared to traditional therapies, concerns about hepatotoxicity and spleen-related complications have arisen. We conducted a retrospective study of 64 HER2-positive metastatic breast cancer patients treated with T-DM1 at our institution. Patients underwent computed tomography or magnetic resonance imaging at baseline and during treatment cycles. Spleen volume, portal vein diameter, and laboratory values were compared between baseline and 12months after T-DM1 treatment. Median spleen volume significantly increased from 201cm3 (IQR, 157-275) at baseline to 291cm3 (IQR, 215-420) after 12months of T-DM1 treatment (P<0.001). Spleen enlargement was observed in 87.5% of patients, while no significant alteration was detected in portal vein diameter. The change in spleen volume was positively correlated with changes in serum globulin levels, liver enzymes, and bilirubin levels, but did not impact survival outcomes. T-DM1 therapy in HER2-positive metastatic breast cancer leads to significant spleen enlargement and systemic biochemical changes. Future studies should focus on elucidating the long-term implications of these findings and optimizing monitoring strategies for spleen-related complications.

8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study

Abstract Disclosure: A.O. Agbaje: None. Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p&amp;lt;0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p&amp;lt;0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p&amp;lt;0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p&amp;lt;0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood. Presentation: 6/1/2024

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.

Longitudinal Analysis of Bone Metabolic Markers and Bone Mechanical Properties in STZ-Induced Diabetic Rats.

Background: This longitudinal study examined the early effects of type 1 diabetes on bone mechanical properties and metabolic markers in mature rats, focusing on the natural progression of diabetes-induced changes without external treatments. Methods: Forty-eight 8-month-old male Wistar rats were divided into two groups, with one group receiving a single dose of streptozotocin (STZ, 60 mg/kg). Assessments were performed 2, 4, and 8 weeks post-administration, including serum biochemical analyses, bone marker assessments, and mechanical bone tests. The data were analyzed using two-way ANOVA to evaluate the impact of time and treatment. Results: At 2 weeks, diabetic rats showed increased fasting blood glucose (p < 0.001), decreased insulin levels (p = 0.03), and changes in HOMA markers (p < 0.001), liver enzymes (p < 0.001), inflammatory markers (p < 0.001), and bone metabolism markers (osteocalcin (p < 0.001), OPG (p = 0.006), RANKL (p < 0.001), and OPG/RANKL ratio (p < 0.001)), with initial alterations in bone geometry. By week 4, decreased body weight in the diabetic group (p < 0.001) led to further changes in bone geometry and initial differences in mechanical properties. At 8 weeks, significant declines in body (p < 0.001) and bone (p < 0.001) weights were observed, along with further deterioration in bone geometry and mechanical properties. Conclusions: The study highlights the significant impact of STZ-induced diabetes on bone health as early as two weeks post-STZ administration, with marked temporal changes in biochemical markers and mechanical properties.

Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial.

Background: Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods: Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan®) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results: After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls (p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions: Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.

Biomagnetismo medicinal na hepatite autoimune: um estudo de caso

Autoimmune Hepatitis (AIH) is a chronic and severe inflammatory disease of the liver caused by loss of tolerance to hepato-specific autoantigens, and the identification is made by applying diagnostic scores. It is characterized by an increase in serum aminotransferases - aspartate aminotransferase (AST) and alanine aminotransferase (ALT), immunoglobulin G, autoantibodies, where triggering agents appear that confuse the immune system that recognizes components of some hepatocytes as antigens. In this study, Medicinal Biomagnetism (BM) was applied, which is a treatment method developed by Dr. Isaac Goiz Durán (1941-2021), whose technique consists of applying a pair of medium intensity magnets -1,000 to 7,500 Gauss, with opposite polarities that resonate with each other and aim to depolarize the dysfunction magnetic field called Biomagnetic Pair (BMP). The magnetic resonance generated by the static magnetic fields, identifies and restores the electron spin of the biochemical elements that support the hydrogenion potential (pH) distortion. The objectives os this study were: to investigate whether there was any change in the clinical and laboratory signs of the patient undergoing BM and to investigate the applicability of the technique in her clinical evolution; compare possible changes in saliva pH before and after therapy; observe whether there were changes in liver enzymes during the treatment period; find out whether during the treatment the hepatologist indicated a reduction in the dosage of the medication in view of the clinical/laboratory improvement; and if there was an improvement in symptons. Through the analysis of the medical records, it was observed that the BM tecnique made it possible to improve the clinical/laboratory status of the patient with AIH.

P194 VERY LOW-DOSE CYPROTERONE ACETATE (12.5 MG/DAY) IS EFFECTIVE AS ANDROGEN BLOCKER; WELL TOLERATED AND NOT ASSOCIATED WITH HYPERTENSION DEVELOPMENT IN YOUNG FEMALE TRANSGENDER PEOPLE

Background and Objective: Cyproterone acetate (CPA) has serious adverse effects (hyperprolactinemia, obesity, depression, thrombogenesis, liver toxicity, meningioma…) but the optimal dose has not been established. CPA is associated with a high risk of hypertension development, even with doses as low as 25 mg/day. We sought to establish if a very low CPA dose (12.5 mg/day) is effective as antiandrogen, its side effect profile, and if it is associated with hypertension development. Methods: Consecutive non-orchidectomized transgender women &lt;30 years were offered CPA 12.5 mg/day instead of the regular 50-100 mg/day dose, along with estradiol (individually titrated); CPA dose was increased to 25 (eventually 50) mg/day if plasma testosterone was &gt;2 nmol/L or there was clinical hyperandrogenism. Body weight, blood pressure, AST, ALT, GGT, prolactin, FSH, LH, estradiol and testosterone were monitored. A matched group of patients with LHRH agonist as antiandrogen plus estradiol served as control. Hypertension was diagnosed according to the current ESH guidelines. All patients gave informed consent. Results: 39 patients were recruited, median follow-up was 2.3 years. 32 were maintained on CPA 12.5 mg/day, two increased to 25 mg/day, one to 50 mg/day, two withdrew due to gender-affirming surgery; one was lost to follow-up. There were no serious side effects or related withdrawals. The control group included 35 patients without significant differences at baseline. Suppression of testosterone, LH and FSH were effective and comparable with the control group but a moderate increase in prolactin was observed (26±12 to 38±22 ng/mL, p=0.034). Neither group had changes in liver enzymes. Blood pressure and body weight did not increase significantly in either group; the incidence of hypertension was low in both groups (1 patient each). Conclusions: Very low-dose CPA was effective and well tolerated as antiandrogen in a large majority of our patients. While CPA is reportedly associated with a striking dose-dependent increase in the incidence of hypertension in the 25-100 mg/day dose-range, the 12.5 mg/day dose appears to be safer.

Impact of Isotretinoin on Blood Lipids and Liver Enzymes: A Retrospective Cohort Study in Saudi Arabia.

Isotretinoin is an effective treatment for acne but can cause side effects such as changes in blood lipids and liver enzymes. Laboratory monitoring is essential during treatment, but there is variation in monitoring practices. This study aims to investigate the relationship between isotretinoin therapy and its effects on complete blood count in Saudi Arabia to improve patient outcomes. The study was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh, Saudi Arabia, between January 2016 and December 2020. Following the inclusion and exclusion criteria, 515 patients were randomly selected for the study. The data was analyzed using SPSS, and descriptive statistics and paired samples t-tests were employed to analyze the data. In this study, 515 patients were enrolled. Of these participants, 76.7% (n=395) were females and 23.3% (n=120) were males. The mean age of the study participants was 23.98±7.4 years and ranged between 16 and 65 years. The mean dose of Isotretinoin administered was 27.65±9.6 mg/day, with a range of 10-60 mg/day. The mean BMI of the study participants was 24.3±4.1 kg/m2, ranging from 14.3 to 44.8 kg/m2. Regarding the effect of Isotretinoin on laboratory measures, significant statistical differences were found in hemoglobin measurements (t=-3.379, p=0.001), platelets (t=-3.169, p=0.002), neutrophils (%) (t=3.107, p=0.002), total cholesterol (t=-13.017, p=0.000), AST (t=-6.353, p=0.000), ALT (t=-4.352, p=0.000), HDL (t=2.446, p=0.015), and LDL (t=-12.943, p=0.000). However, there were no significant statistical differences in the measurements of WBC, neutrophils (count), or triglycerides. In the Chi-square analysis and Fisher's Exact test to identify the interaction between BMI, dose, and gender on abnormal lab results, significant interaction was found between participants' BMI and abnormal HDL measurements (p=0.006). Furthermore, there were significant interactions between Isotretinoin dose (either less than 30 mg/day or 30 mg/day or more) and abnormal neutrophil count (p=0.04), abnormal HDL measurements (p=0.010), and abnormal triglycerides measurements (p=0.020). Moreover, a statistically significant interaction was found between participants' gender and abnormal hemoglobin measurements (p=0.006), abnormal total cholesterol (p=0.016), abnormal AST measurements (p=0.001), abnormal ALT measurements (p=0.000), abnormal HDL measurements (p=0.000), and abnormal triglycerides measurements (p=0.007). In conclusion, the study found that isotretinoin therapy has significant effects on several laboratory measures, including hemoglobin, platelets, neutrophils, total cholesterol, AST, ALT, HDL, and LDL. The study also revealed significant interactions between BMI, dose, gender, and abnormal lab results.

13-Week repeated-dose toxicity study of optimized aqueous extract of Moringa oleifera leaves in mice

Ethnopharmacological relevanceMoringa oleifera (Moringaceae family), commonly known as horseradish or tree of life, is traditionally used for various diseases, such as diabetes, hypercholesterolemia, neurological disorders, among others. Aim of the studyTo evaluate the toxicological profile of the oral use of an aqueous extract of Moringa oleifera leaves for 13 weeks in mice. Materials and methodsInitially, a factorial design (23) was carried out to optimize aqueous extraction using as variables; the extraction method and proportion of drug. The 13-week repeated-dose toxicity trial used female and male mice, with oral administration of aqueous extract of Moringa oleifera leaves at doses of 250, 500, and 1000 mg/kg. The animals were evaluated for body weight, water and feed intake, biochemical and hematological parameters, urinalysis, ophthalmology and histopathology of the liver, spleen and kidneys. ResultsThe extraction efficiency was evidenced by the extraction by maceration at 5%, obtaining the optimized extract of Moringa oleifera (OEMo). The oral administration of OEMo did not promote significant difference (p > 0.05) in the weight gain, food and water consumption of the control animals and those treated with 250 and 500 mg/kg. However, treatment with 1000 mg/kg promoted a reduction (p < 0.05) in food intake and body weight from the 7th week onwards in male and female mice. No alterations were detected in the hematological and histological parameters in the concentrations tested for both sexes. The highest concentration treatment (1000 mg/kg) promoted an increase in transaminases in males and females. All concentrations promoted a significant decrease (p < 0.05) in the serum lipid profile of mice. ConclusionThis study developed an optimized extract of Moringa oleifera leaves, which should be used with caution in preparations above 500 mg/kg for the long term because it leads to significant changes in liver enzymes. On the other hand, the extract proved to be a promising plant preparation for hyperlipidemia in mice.

Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Pancreatic pseudotumor due to peripancreatic lymphadenitis: case report and literature review

The pancreas has exocrine and endocrine glandular tissue, the latter accounting for only 1-2% of the gland. Pancreatic disorders are common but difficult to diagnose due to their anatomical location and vague symptoms. Pancreatic pseudotumors are enlarged pancreas without neoplasia and can be mistakenly diagnosed as malignant, complicating treatment. One study demonstrated that 9.2% of pancreatic resections suspected of malignancy were benign. In the clinical case presented, a 35-year-old male patient presented with severe abdominal pain, jaundice, weight loss, as well as fever, nausea, and vomiting. Laboratory tests showed significant changes in liver enzymes, bilirubin, and blood count. The differential diagnosis included lymphoma, tuberculosis, and other pathologies. Laparotomy revealed peripancreatic lymph nodes with caseous necrosis, which were confirmed as tuberculosis. Pancreatic tuberculosis is rare and can be confused with neoplasms due to similar symptoms. Accurate diagnosis requires a high degree of suspicion and methods such as image-guided biopsy. Treatment involves the use of tuberculostatics. In endemic regions, tuberculosis should always be considered in cases of peripancreatic lesions.

Analysis of Probiotic Role in Non-Alcoholic Fatty Liver Disease (NAFLD) Management: A Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing global health problem. Probiotics have emerged as a potential therapy for NAFLD, but evidence for their efficacy remains mixed. This meta-analysis aims to evaluate the effectiveness of probiotics in the management of NAFLD. Methods: A comprehensive literature search was performed on PubMed, Embase, Cochrane Library, and Web of Science databases until December 2023. Randomized controlled trials (RCTs) evaluating the effects of probiotics in NAFLD patients were included. The main outcomes evaluated were changes in liver enzymes (ALT, AST), insulin resistance index (HOMA-IR), and hepatic steatosis score. Meta-analysis was performed using a random effects model, and heterogeneity was assessed using the I² statistic. Results: Twenty-five RCTs involving 1845 patients met inclusion criteria. Meta-analysis showed that probiotics significantly reduced ALT (MD -8.45; 95% CI -12.67 to -4.23; p&lt;0.0001) and AST (MD -6.89; 95% CI -10.11 to -3.67; p&lt;0.0001) levels compared with placebo. Significant reductions were also observed in HOMA-IR (MD -0.68; 95% CI -1.02 to -0.34; p&lt;0.0001) and hepatic steatosis scores (SMD -0.45; 95% CI -0.71 to -0.19; p=0.0008). Subgroup analysis showed that the effects of probiotics were more pronounced in patients with NAFLD non-alcoholic steatohepatitis (NASH) and those receiving multi-strain probiotics. Conclusion: This meta-analysis provides strong evidence that probiotics have beneficial effects on biochemical and imaging parameters in NAFLD patients. Probiotics may be considered as an adjunct therapy for NAFLD, especially in patients with NASH. However, more research is needed to determine the optimal probiotic strain, dosage, and duration of treatment.

Assessing the Efficacy of Farnesoid X Receptor Agonists in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis

Background: Several randomized clinical trials have been conducted assessing the potential efficacy of X receptor (FXR) agonists in patients with metabolic dysfunction-associated liver disease (MASLD). A comprehensive review and analysis were needed to evaluate the findings of these trials. Hence, this systematic review and meta-analysis aim to study the association between FXR agonists and hepatic outcomes in patients with MASLD. Introduction: Metabolic dysfunction-associated liver disease (MASLD) involves abnormal lipid accumulation in the liver, potentially progressing to metabolic dysfunction-associated steatohepatitis (MASH) with severe outcomes. X receptors (FXR), activated by bile acids, regulate liver metabolism and inflammation, offering a promising therapeutic target. Clinical trials with FXR agonists like obeticholic acid and tropifexor show potential in improving MASH histology. However, a comprehensive analysis of FXR modulation’s impact on liver pathology and metabolism in MASLD and MASH is lacking. This systematic review aims to address this gap, informing future therapeutic approaches. Methods: Systematic review and meta-analysis evaluating the efficacy of FXR agonists in 1,227 patients assigned to the FXR intervention group compared to 650 patients in the placebo group. Changes in liver enzymes and hepatic steatosis assessed by MRI-PDFF were evaluated. Results: FXR agonist use was associated with a significant reduction in levels of AST, (WMD= -4.51, 95% CI=[-8.39,-0.63], P=0.02); ALT (WMD= -13.02, 95% CI=[-17.85,-8.19], P&lt;0.00001); GGT (WMD= -32.20, 95% CI=[-38.63,-25.98], P&lt;0.00001); MRI-PDFF, (SMD= -1.14, 95% CI=[-1.92,-0.35], P=0.005). FXR agonists did not significantly affect ALP levels, (WMD= 25.04, 95% CI= [19.22,30.87], P&lt;0.00001}. Conclusions: Results show promising evidence supporting the efficacy of FXR agonists in reducing hepatic steatosis and biomarkers of hepatic injury such as ALT, AST, and GGT.

Changes in glucose metabolism, C-reactive protein, and liver enzymes following intake of NAD + precursor supplementation: a systematic review and meta‐regression analysis

BackgroundThere are contradictory effects regarding the effect of NAD + precursor on glucose metabolism and liver enzymes. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD + precursor supplementation on glucose metabolism, C-reactive protein (CRP), and liver enzymes.MethodsPubMed/MEDLINE, Web of Science, SCOPUS, and Embase databases were searched using standard keywords to identify all controlled trials investigating the glucose metabolism, CRP, and liver enzymes effects of NAD + precursor. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes.ResultsForty-five articles with 9256 participants’ were included in this article. The pooled findings showed that NAD + precursor supplementation had a significant increase in glucose (WMD: 2.17 mg/dL, 95% CI: 0.68, 3.66, P = 0.004) and HbA1c (WMD: 0.11, 95% CI: 0.06, 0.16, P < 0.001) as well as a significant decrease in CRP (WMD: -0.93 mg/l, 95% CI -1.47 to -0.40, P < 0.001) compared with control group, and was not statistically significant with respect to insulin and homeostasis model assessment of insulin resistance (HOMA-IR). However, we found no systemic changes in aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase (ALP) levels after NAD + precursor supplementation. The results of the subgroup analysis showed that the intake of NAD + precursor during the intervention of more than 12 weeks caused a greater increase in the glucose level. Furthermore, Nicotinic acid supplementation (NA) causes a greater increase in glucose and HbA1c levels than nicotinamide (NE) supplementation.ConclusionsOverall, these findings suggest that NAD + precursor supplementation might have an increase effect on glucose metabolism as well as a decrease in CRP.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

BACKGROUND AND AIMPorto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension (PH). Liver biopsy (LB) is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyl transferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. METHODSThe study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021. RESULTS144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only twelve (8.3%) had liver stiffness measurements (LSM) >10 kPa, 7 (4.8%) had ultrasound PH evidence. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%). Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio, OR = 2.60, 95% confidence interval, CI: 1.13-5.99), LSM < 10 kPa (OR = 11.05, 95% CI: 2.16-56.66) and GGT < 200 U/L (OR = 2.69, 95% CI: 1.22-5.98). CONCLUSIONSPSVD was the main cause of persistent and unexplained elevation of GGT. Male sex, LSM < 10kPa and GGT < 200U/l were associated with PSVD. These findings highlight the role of LB in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation. IMPACT AND IMPLICATIONSIn outpatient settings, it is common to encounter subjects with persistent and unexplained GGT elevation. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder (PSVD) among these subjects when they undergo liver biopsy. Male sex, liver stiffness measurement (LSM) < 10 kPa, and GGT < 200 IU/L predict this histological finding.These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension (PH). Additionally, the data may encourage further studies in the field of PSVD, particularly to define its clinical evolution in patients without signs of PH at diagnosis.

Immediate Effects of Anesthesia Agents on Liver Function

Anesthetic agents and types may deteriorate liver function; therefore, choosing anesthetics with less hepatotoxicity is important. The elevations of serum aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels are frequently observed after surgical procedures, whether performed under general or spinal (regional) anesthesia. Therefore, the study aimed to investigate and compare the changes in liver enzymes following general anesthesia and regional anesthesia. An observational sheet was used to obtain data from patients and then statistically analyzed using the IMB Statistical Package for Social Sciences (SPSS) Statistic software version (23). A significant difference in the liver enzymes levels change was determined with a p-value of &lt; 0.05. it was observed that in both groups of general and regional anesthesia, the level of AST, ALT, and ALP enzymes was significantly elevated post-operative compared to pre-operative with (P=0.000), especially in the level of ALT enzyme. The current study indicated that both general and regional anesthesia caused increased liver enzymes.

BRIDGE to liver health: implementation of a group telehealth psychoeducational program through shared medical appointments for MASLD management

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) represents a significantly costly and increasingly prevalent disease, with treatment focused on lifestyle intervention. Integrating education and behavioral health into clinical care offers opportunities to engage and empower patients to prevent progression of liver disease. We describe the design and implementation of Behavioral Resources and Intervention through Digital Group Education (BRIDGE), a 6-session group telehealth program led by advanced practice providers (APPs) in 90-min shared medical appointments (SMAs) with small groups of MASLD patients in an academic outpatient hepatology clinic. The program contains multi-component group interventions, with didactic education and behavioral coaching, while leveraging peer-based learning and support.MethodsA mixed-methods exploratory pilot study was conducted. Feasibility and acceptability of the clinical intervention were assessed by tracking recruitment, attendance, and retention of BRIDGE participants, patient interviews, and debriefing of clinician and staff views of the clinical program. Implementation metrics included program development time, workflow and scheduling logistics, and billing compliance for sustainability. Finally, patient parameters including changes in liver enzymes, FIB-4, weight, and BMI from pre- to post-BRIDGE were retrospectively analyzed.ResultsWe included 57 participants (median age 57, interquartile range (IQR) 50 – 65 years), 38 (67%) female, 38 (67%) white, and 40% had public insurance. Thirty-three (58%) participants completed all six sessions, while 43 (75%) attended at least five sessions. Patients who completed all sessions were older (median age 61 vs 53.5; p = 0.01). Gender, race/ethnicity, and insurance type were not significantly associated with missed sessions, and patients had similar rates of completion regardless of weight, BMI, or stage of liver disease. Barriers to completion included personal illness, family reasons, work commitments, or insurance issues. Prior to BRIDGE, median BMI was 31.9 (SD 29 – 36), with a median weight loss of 2 pounds (IQR -2 – 6) after BRIDGE.ConclusionThe BRIDGE telehealth SMA program was feasible, well-attended, and positively reviewed. This pilot study informs future iterations of program development and evaluation of outcome measures.

Accelerometer-based sedentary time and physical activity with MASLD and liver cirrhosis in 2684 British adolescents

Evidence on the long-term relationship of sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous PA (MVPA) with liver steatosis, fibrosis, cirrhosis, and changes in liver enzymes in the paediatric population is limited. This study examined the associations of cumulative ST, LPA and MVPA from childhood with longitudinal changes in liver indices and enzymes. From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-points accelerometer-measured ST, LPA and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography and staged as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), the prevalence of liver steatosis at age 17 years was 2.6% and 20.5% at age 24 years. The cumulative 1-minute/day increase in ST from ages 11–24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002–1.005] p < 0.001) and severe liver steatosis (1.001 [1.001–1.002] p = 0.002) at age 24 years. Increased ST from childhood was directly associated with progressively increased ALT, AST and GGT from ages 17 to 24 years. Cumulative 1-min/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990–0.991] p < 0.001) and severe liver steatosis (0.999 [0.998–0.999] p < 0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-min/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994–0.998] p < 0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. In conclusion, increasing LPA, sustaining MVPA and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and liver cirrhosis by young adulthood.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.