Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and valuation-assessed Systematic Review and Dose-Response Meta-analysis.

PURPOSE: Even though various randomized controlled trials (RCTs) have assessed the effect of propolis on glycemic indices and liver enzyme concentrations in adults, results have been inconsistent, without conclusive evidence. This systematic review and meta-analysis of RCTs sought to evaluate the effects of propolis consumption on glycemic indices and liver enzymes, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase in adults. METHODS: Two independent researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library for English-language RCTs published up to April 2024. The results were generated through a random-effects model and presented as the weighted mean difference (WMD) with a 95% CI. The Cochrane Risk of Bias Tool for RCTs and Grading of Recommendations Assessment, Development, and Evaluation assessment were used to evaluate quality assessment and certainty of evidence. FINDINGS: A total of 21 RCTs were included. A pooled analysis of 24 trials reported that propolis consumption led to a significant reduction in fasting blood glucose (WMD, -9.75 mg/dL; 95% CI, -16.14 to -3.35), insulin (WMD, -1.64 µU/mL; 95% CI, -2.61 to -0.68), glycosylated hemoglobin (WMD, -0.46%; 95% CI, -0.71 to -0.21), homeostatic model assessment of insulin resistance (WMD, -0.54; 95% CI, -0.98 to -0.09), alanine transaminase (WMD, -2.60 IU/L; 95% CI, -4.58 to -0.61), and aspartate aminotransferase (WMD, -2.07 IU/L; 95% CI, -3.05 to -1.09). However, there were no significant effects on gamma-glutamyl transferase in comparison with the control group. IMPLICATIONS: This meta-analysis has shown that propolis supplementation may have beneficial effects on glycemic indices and liver enzymes. Future high-quality, long-term RCTs are needed to confirm our results. CLINICALTRIALS: gov identifiers: CRD42024524763. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

New biomarkers for liver involvement by dengue infection in adult Vietnamese patients: a case-control study.

Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels (< 80, 80-400, > 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80-400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (< 80 U/L). There was a good correlation between AST, alanine aminotransferase enzyme (ALT), and the new liver biomarkers such as GLDH, αGST, ARG-1, and HPPD. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. Moreover, these new biomarkers should be investigated further to explain the pathogenesis of dengue and to validate their prognostic utility.

Efficacy of Probiotics on Improvement of Health Outcomes in Cirrhotic Liver Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Liver cirrhosis is a chronic condition of the liver and is the 14th most common cause of death around the world; yet it remains an incurable disease. Probiotics have gained significant popularity as a potential treatment option for liver cirrhosis. METHODS: A systematic review and meta-analysis was conducted to assess the effects of probiotics on liver cirrhosis. PubMed, Scopus, Cochrane Central Register for Controlled Trials (CENTRAL) and ProQuest Dissertation and Thesis were searched from 2000 to January 2024 for studies that evaluated the effects of probiotics on a variety of outcomes of liver disease. RESULTS: A total of 22 randomised controlled trial studies were included in the meta-analysis. Probiotics significantly decreased Gamma-glutamyl transferase (effect size: -0.307, p=0.024, 95% CI [-0.572, -0.040]) and Aspartate aminotransferase (p=0.013, 95% CI [-17.927, -2.128]). Significant reduction in serum ammonia levels (effect size= -1.093, p= 0.000, 95% CI [-1.764, -0.423]) and endotoxin levels (effect size= -0.961, p=0.000, 95% CI [-1.537, -0.385]) were also found. SUMMARY: Overall probiotics could be recommended as a potential adjunct therapy for patients with cirrhosis, as they appear to have some benefit in improving liver function, and are well tolerated with minimal adverse effects. More comprehensive research with larger sample sizes is recommended to understand more about the widespread effects of probiotic use.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Effect of Diets with the Addition of Edible Insects on the Development of Atherosclerotic Lesions in ApoE/LDLR-/- Mice.

Foods enriched with insects can potentially prevent several health disorders, including cardiovascular diseases, by reducing inflammation and improving antioxidant status. In this study, Tenebrio molitor and Gryllus assimilis were selected to determine the effect on the development of atherosclerosis in ApoE/LDLR-/- mice. Animals were fed AIN-93G-based diets (control) with 10% Tenebrio molitor (TM) and 10% Gryllus assimilis (GA) for 8 weeks. The nutritional value as well as antioxidant activity of selected insects were determined. The lipid profile, liver enzyme activity, and the fatty acid composition of liver and adipose tissue of model mice were evaluated. Quantitative analysis of atherosclerotic lesions in the entire aorta was performed using the en face method, and for aortic roots, the cross-section method was used. The antioxidant status of the GA cricket was significantly higher compared to the TM larvae. The results showed that the area of atherosclerosis (en face method) was not significantly different between groups. Dietary GA reduced plaque formation in the aortic root; additionally, significant differences were observed in sections at 200 and 300 µm compared to other groups. Furthermore, liver enzyme ALT activity was lower in insect-fed groups compared to the control group. The finding suggests that a diet containing edible insect GA potentially prevents atherosclerotic plaque development in the aortic root, due to its high antioxidant activity.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Neonatal Graves Disease Masquerading as Hemochromatosis.

Thyroid autoimmunity is extremely common in the adult population and can affect pregnancy outcomes. Signs in the newborn can range from absent to severe, making the diagnosis easy to miss. We present an interesting case of neonatal Graves disease associated with intrauterine growth restriction, premature delivery, and liver failure with severely high ferritin, thought to be secondary to hemochromatosis. Treatment of the underlying hyperthyroidism caused a rapid resolution of the elevated ferritin and liver failure. This report highlights the importance of considering Graves disease in newborns with liver failure of unknown etiology.

Fetal gender prediction by monitoring circulating steroid hormones and some biochemical parameters in maternal dromedary camels.

To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.

An Observational Study to Find the Association of Viral Load, NS1 Antigen, IgG Antibody, and Other Laboratory Parameters With the Outcome of Dengue Patients in Eastern India.

Background Dengue, the mosquito-borne febrile disease caused by the dengue virus, has become one of the major concerns of public health. It may present with only fever, or there may be a hemorrhagic manifestation or septic shock. As there is no specific treatment for dengue, early detection of the disease, assessment of progression, and prediction of outcome by studying the laboratory markers will help guide the management of cases and lower morbidity and mortality. Methodology This clinico-observational study was conducted at the Department of Microbiology in a tertiary care hospital in Kolkata, India, from February 2020 to August 2022 to determine the outcome of dengue patients in correlation with viral load, NS1 antigen, IgM and IgG antibodies, ferritin level, platelet count, and other laboratory parameters. Results Out of 316 samples from fever patients, 103 (32.5%) were NS1 antigen reactive. We followed up the dengue patients (n = 103) for 15 days and divided them into three groups according to their duration of symptoms (group A suffered for ≤5 days, group B for 5 to 10 days, and group C for >10 days) and per the WHO classification of disease severity, namely dengue without warning signs (DOS), dengue with warning signs (DWS), and severe dengue (SD). Based on severity, 65 (63.1%) patients had DOS, whereas 31 (30.09%) patients had DWS, and seven (6.79%) patients had SD. Secondary infection was present in 83.33% of patients in group C, 71% of DWS cases, and 57% of SD cases, which positively correlates with liver enzymes, viral load (mean value 102195 in secondary infection vs. 1195 copies/10 µl in primary infection), and negatively correlates with platelet counts (mean value 60,213 in secondary infection vs. 1,25,516 in primary infection). Patients in group C had higher liver enzymes, a lower platelet count, and a higher initial viral load than groups A and B. Similarly, SD cases had a higher ferritin level (9215 ug/l), a lower platelet count (mean value 23,250), and a higher initial viral load (mean value 2,74,257 copies/10 µl). An increase in hematocrit value considering the peak value and its baseline value is an important marker for disease severity rather than its absolute value. Conclusion Poor outcome of dengue infection, i.e., an increase in the duration of symptoms and disease severity depends on concurrent associations between high serum ferritin, increased hematocrit level, thrombocytopenia, secondary infection, increasing liver enzymes, and increased initial viral load.

Effects of Thymbra spicata extract and Thymol on morphine withdrawal syndrome in mice (insights to the liver function, antioxidant, and behavioral responses).

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans.

Evaluation of elevated serum liver enzymes and metabolic syndrome in the PERSIAN Guilan cohort study population.

Objective: The purpose of this study is to evaluate the association between elevated serum liver enzymes and Metabolic Syndrome (MetS) in Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study (PGCS) population. Methods: This cross-sectional study involved 10,519 individuals between the ages of 35 and 70 enrolled in the PGCS. The gathered data encompassed demographic information, anthropometric measurements, blood pressure, and biochemical indicators. MetS was defined by the National Cholesterol Education Program-Adult Treatment Panel III criteria (NCEP-ATP III). The associations between elevated liver enzymes and MetS were examined using logistic regression analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated. Results: The prevalence of MetS was 41.8 %, and the prevalence of elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were 19.4, 4.6, 11.6, and 5.1 %, respectively. In the unadjusted model, elevated ALT, AST, and GGT were associated with increased odds of MetS (OR = 1.55, 95 % CI: 1.41-1.71; OR = 1.29, 95 % CI: 1.07-1.55, and OR = 1.90, 95 % CI: 1.69-2.14, respectively). These associations remained significant for ALT and GGT after adjustment for some demographic and clinical characteristics (aOR = 1.31, 95 % CI: 1.17-1.46 and aOR = 1.30, 95 % CI: 1.14-1.49, respectively). In addition, the odds of MetS increased with the number of elevated liver enzymes, up to almost 1.32-fold among subjects with three/four elevated liver enzymes. Conclusion: The higher incidence of elevated liver enzymes was associated with an increased likelihood of MetS. Including liver markers in diagnosing and predicting MetS holds promise and is considered a possible approach.

Potential of Liver Serum Enzymes and SUVmax in Primary Tumors as Predictive Biomarkers With Correlational Evidence.

Introduction Cancer exerts a substantial influence on the body's metabolism through varied mechanisms, instigating a metabolic reprogramming that maintains the unchecked growth and survival of cancer cells, consequently perturbing diverse metabolic parameters. The introduction of positron emission tomography-computed tomography (PET/CT), delivering detailed insights into both metabolic and morphological aspects, has brought about a revolutionary shift in modern cancer detection. Exploring the potential connection between PET-CT metabolic features and the metabolic parameters of liver enzymes in an individual can unveil novel avenues for cancer diagnosis and prognosis. Materials and methods This study conducted a retrospective analysis of patient records from our institution, covering the period from January 2021 to September 2023, focusing on individuals with various malignancies. The data included information on gender, age, clinical history, and liver serum parameters, which were compiled into tables. Additionally, inflammatory indicators such as ALT (alanine transaminase), ALP (alkaline phosphatase), total protein (TP), ALT/AST ratio, and SUVmax were collected and plotted. The study used Pearson correlation analysis to assess the relationship between each inflammatory variable and SUV (max) as determined by PET-CT. Results In breast cancer, there was a statistically significant positive correlation (R2=0.0651) between serum ALP levels and SUVmax as determined by regression analysis. Hodgkin lymphoma, on the other hand, showed a statistically significant negative correlation between the ALT-to-AST ratio (ALT/AST) and SUVmax (r = -0.45, R2 = 0.204). In non-Hodgkin lymphoma patients, total protein (TP) was negatively correlated with SUVmax (R2=-0.081, r= -0.28), while in lung cancer patients, there was a significant positive correlation with regression correlation coefficients (R2 = 0.026, 0.024, 0.024, and 0.018 for ALT/AST, TP, ALP, albumin, and ALT, respectively). Conclusion Aligning with these results, it can be a recent addition to acknowledge that both the tumor metabolic parameter (SUVmax) and the levels of liver serum enzymes exhibit a potential for predicting patient prognosis in various cancers.

Associations of adipose insulin resistance index with leg (gluteofemoral) fat (inverse) and serum alanine aminotransferase (positive) in young Japanese women.

Aim: Associations of the adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acid) with body fat distribution and the ratio of alanine to aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, were examined in the context of the metabolic syndrome. Methods: Legs, the trunk and body fat by DXA, blood pressure (BP) and blood chemistry were measured in 284 young Japanese female university students and 148 middle-aged biological mothers whose BMI averaged <23 kg/m2. Results: Young women had higher leg fat/body fat and lower trunk fat/body fat ratio (both p < 0.001) compared with middle-aged women but AT-IR did not differ between the two groups. We had multivariable linear regression analysis for AT-IR as a dependent variable including leg fat/body fat ratio, trunk fat/body fat ratio, fasting glucose, triglyceride, HDL cholesterol and systolic BP as independent variables. Leg fat/body fat ratio, fasting glucose and triglyceride (p = 0.013, 0.009 and 0.016, respectively) emerged as determinants of AT-IR in young women. Trunk fat/body fat ratio and fasting glucose (p = 0.003 and 0.019, respectively) emerged in middle-aged women. In a model which included ALT/AST as an additional independent variable, ALT/AST (p = 0.016) was the fourth independent determinant in young women and the single determinant of AT-IR in middle-aged women (p < 0.001). Conclusion: In young Japanese women, adipose tissue insulin resistance was associated with reduced leg fat, a subtle partial lipodystrophy-like phenotype associated with reduced adipose tissue expandability. It was associated with elevated trunk (abdominal) fat in middle-aged women and with ALT/AST, a marker of hepatosteatosis, in two groups of Japanese women, suggesting ectopic fat deposition associated with reduced adipose tissue expandability.

Acute onset nitrofurantoin-induced autoimmune hepatitis after urinary tract infection treatment.

Key Clinical Message: This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures for treating UTI. Abstract: Various drugs can induce immune-mediated liver damage and in rare instances may lead to autoimmune hepatitis. Here we report an 84-year-old woman who developed autoimmune hepatitis less than 3 weeks after treatment for urinary tract infection with the antibiotic nitrofurantoin. She presented with jaundice, right upper quadrant abdominal pain, nausea, and vomiting. In the absence of a history of an autoimmune disorder or elevated liver enzymes in the past; elevated liver enzymes after a short course of Nitrofurantoin and the presence of smooth muscle antibodies strongly suggested autoimmune hepatitis, which was confirmed through biopsy sample analysis. The patient scored 7 points on the Naranjo adverse reaction probability scale. The patient's rapid recovery within 1 month of prednisone therapy supports the association of liver damage with nitrofurantoin use.

Ameliorative Effect of Faidherbia albida Against 2.4-Dinitrophenylhydrazine Induced Hyperbilirubinemia in Wistar Albino Rats.

Background: Faidherbia albida, popularly known as gawo in Hausa, is traditionally used to treat jaundice in Zuru emirate of Kebbi State. Herein, the ameliorative effect of F. albida against 2.4-dinitrophenylhydrazine-induced hyperbilirubinemia in Wistar albino rats was investigated. Methods: Thirty healthy rats were administered 75 mg of 2.4-dinitrophenylhydrazine to induce hyperbilirubinemia. Thereafter, groups 1-3 received 500, 750, and 1000 mg/kg body weight of the methanol stem-bark extract, and 15 mg/kg of phenobarbitone (standard drug) was administered to group 4. Groups 5 and 6 served as the untreated and normal controls, respectively. The phytochemical composition was evaluated using standard methods, and acute oral toxicity was evaluated using standard OECD 2008 guidelines. Results: Phytochemical analysis revealed the presence of alkaloids, phenols, and a substantial amount of tannins. A significant (P<0.05) reduction of direct bilirubin, total bilirubin, and total protein levels for all the doses of the extract and standard drug compared to untreated groups was observed. Similarly, there were significant reductions in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels of the group treated with the standard drug and all extract-treated groups compared to elevated levels observed in untreated controls. However, a significant (P<0.05) increase in serum albumin (ALB) levels, red blood cells, hemoglobin, and pack cell volume was observed in all extract-treated compared to the untreated control in contrast to a significant decrease in MCH levels in treated groups compared to the untreated group. Conclusion: F. albida ameliorated the hyperbilirubinemia induced by 2.4-dinitrophenylhydrazine in Wistar albino rats, thus providing some support for its use in traditional medicine to treat jaundice.

Effect of sustained decreases in sedentary time and increases in physical activity on liver enzymes and indices in type 2 diabetes.

Background: Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes. Methods: Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer. Results: Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers. Conclusion: A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

The relationship between liver enzymes, prehypertension and hypertension in the Azar cohort population.

BACKGROUND: The incidence of hypertension (HTN) as a worldwide health problem is rising rapidly. Early identification and management of pre-HTN before HTN development can help reduce its related complications. We evaluated the relationship between liver enzymes levels and pre-HTN/HTN in the Azar cohort population. METHOD: This cross-sectional study was based on data from the large Azar cohort study and a total of 14,184 participants were included. Pre-HTN and HTN were defined based on the American Heart Association guideline. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) levels were measured by Pars Azmoon kits. The relationship between pre-HTN/HTN and liver enzyme levels was evaluated by logistic regression. RESULTS: Of 14,184 participants, 5.7% and 39.6% had pre-HTN and HTN, respectively. In the adjusted model, AST levels of 19-23 IU/l were associated with an elevated risk of pre-HTN (OR [95% CI]: 1.24 [1.04-1.48]). A dose-response increase was seen in pre-HTN in relation to ALT, with the highest OR in the third tertile (1.34 [1.09-1.63]). The odds of pre-HTN also increased with GGT in the third tertile (1.25[1.03-1.52]). In addition, the odds of HTN increased with increased levels of AST, ALT, ALP, and GGT, such that the highest ORs were recorded in the third tertile (OR 1.22 [1.09-1.37], 1.51 [1.35-1.70], 1.19 [1.07-1.34], and 1.68 [1.49-1.89], respectively). Among these enzymes, GGT had the highest OR regarding HTN. CONCLUSION: This study indicates that AST, ALT, ALP and GGT levels were associated with pre-HTN (except for ALP) and HTN, independent of known risk factors. Hence, it may be possible to use liver enzymes to predict the incidence of pre-HTN and HTN, empowering primary care providers to make the necessary interventions promptly.

Moderate Alcohol Consumption Increases the Risk of Clinical Relapse in Male Depressed Patients Treated with Serotonin-Norepinephrine Reuptake Inhibitors.

BACKGROUND: While depression can be associated with multiple comorbidities, the association between depression and liver injury significantly increases the mortality risk. The aim of this study was to evaluate if moderate alcohol intake affects the rate of clinical relapses in patients treated with antidepressants as monotherapy. METHODS: We assessed, over a period of 30 months, the clinical records of 254 patients with depressive disorder, of either gender, without additional pathologies, receiving monotherapy treatment with antidepressants. Thirty-three patients with alcohol abuse, alcoholism or significant cognitive impairment were excluded. The medical and psychiatric history, medication and liver enzyme values were collected and analyzed. RESULTS: Out of the 221 patients who met the inclusion criteria, 78 experienced relapses of depression. The rate of relapse did not correlate with the levels of liver enzymes. Alcohol consumption, as objectified based on GGT levels and the AST/ALT ratio, suggested that men had higher alcohol intake compared to women. Patients treated with serotonin-norepinephrine reuptake inhibitors (SNRIs) with elevated AST levels were approximately 9 times more likely to relapse, while the ones with elevated GGT had a 5.34 times higher risk. While GGT levels remained a marker for relapse in men with elevated GGT, ALT and not AST proved to be a better risk indicator for relapses in male patients. CONCLUSION: The use of SNRIs in depressed male patients with moderate alcohol intake should be carefully considered, as they might be susceptible to higher risks of relapse compared to alternative antidepressant therapies.

The effects of meal patterns on liver steatosis, fibrosis, and biochemical factors in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial.

Background: This study was designed to compare the effects of four meal patterns on liver steatosis, fibrosis, and biochemical factors in patients with Nonalcoholic fatty liver disease (NAFLD). Methods: The 12-week intervention was performed on 123 patients with NAFLD who were randomly allocated into four groups: "3-meals", "skipping breakfast", "skipping dinner", and " 3 meals and 3 snacks per day." group. The assessment of liver steatosis, fibrosis, biochemical factors, and anthropometrical evaluation were performed at baseline and at end of the study. Results: A significant improvement was found in the liver steatosis and fibrosis among the patients who consumed 3 meals, 3 snacks compared to the other groups (P < 0.001). In addition, a higher reduction was observed in serum levels of alanine amino transferase (ALT) (20.93 ± 23.37 mg/dl, P < 0.001), aspartate aminotransferase (AST) (17.15 ± 16.48 mg/dl, P < 0.001), gamma-glutamyl transferase(GGT) (13.43 ± 13.41 mg/dl; P < 0.001), and alkaline phosphatase (ALK) (47.19 ± 60.51 mg/dl; P = 0.004) in patients who consumed 3 meals, 3 snacks, while the concentration of liver enzymes in patients who consumed 3 meals increased significantly. At the end of the study, there was a significant increase in the fasting blood sugar (FBS) concentration in the "skipping breakfast" group (17.51 ± 38.85 mg/dl; P = 0.011) and "3-meals" group (17.51 ± 38.85 mg/dl, P = 0.03). Conclusion: Consuming 3 meals, 3 snack per day significantly improves disease severity and biochemical factors in NAFLD patients. Further studies are warranted. Trial registration number: : IRCT20201010048982N2. Name of the registry: Urmia University of Medical Sciences. Date of registration: 2021-08-22, 1400/05/31. URL of trial registry record: https://www.irct.ir/search/result?query=IRCT20201010048982N2. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01375-2.