Decreased Alanine Aminotransferase Research Articles

Changes in laboratory results in transgender individuals on hormone therapy - a retrospective study and practical approach.

Interpreting laboratory results for transgender individuals who started hormone therapy requires careful consideration, specifically for analytes that have sex-specific reference intervals. In literature, conflicting data exist on the effect of hormone therapy on laboratory parameters. By studying a large cohort, we aim to define what reference category (male or female) is most appropriate to use for the transgender population over the course of gender-affirming therapy. A total of 2201 people (1178 transgender women and 1023 transgender men) were included in this study. We analyzed hemoglobin (Hb), hematocrit (Ht), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), creatinine, and prolactin, at three different time points: pretreatment, during hormone therapy, and after gonadectomy. For transgender women, Hb and Ht levels decrease after initiation of hormone therapy. The concentration of liver enzymes ALT, AST, and ALP decrease whereas the levels of GGT do not change statistically significantly. Creatinine levels decrease whereas prolactin levels rise in transgender women during gender-affirming therapy. For transgender men Hb and Ht values increase after starting hormone therapy. Liver enzymes and creatinine levels increase statistically significant as well upon hormone therapy while prolactin concentrations decrease. Overall, reference intervals in transgender people after 1 year on hormone therapy resembled those of their affirmed gender. Generating transgender-specific reference intervals is not essential to correctly interpret laboratory results. As a practical approach, we recommend to use the reference intervals of the affirmed gender from 1 year onwards after starting hormone therapy.

Naringin protects against inflammation and apoptosis induced by intestinal ischemia-reperfusion injury through deactivation of cGAS-STING signaling pathway.

Effective amelioration of ischemia/reperfusion (I/R)-induced intestinal injury and revealing its mechanisms remain the challenges in both preclinic and clinic. Potential mechanisms of naringin in ameliorating I/R-induced intestinal injury remain unknown. Based on pre-experiments, I/R-injured rat intestine in vivo and hypoxia-reoxygenation (H/R)-injured IEC-6 cells in vitro were used to verify that naringin-alleviated I/R-induced intestinal injury was mediated via deactivating cGAS-STING signaling pathway. Naringin improved intestinal damage using hematoxylin and eosin staining and decreased alanine aminotransferase and aspartate aminotransferase contents in plasma. Naringin decreased inflammation characterized by reducing IL-6, IL-1β, TNF-α, and IFN-β contents in both plasma and IEC-6 cells. Naringin mitigated oxidative stress via recovering superoxide dismutase, glutathione, and malondialdehyde levels in the I/R-injured intestine. Naringin reduced the expression of apoptotic proteins, including Bax, caspase-3, and Bcl-2, and reduced terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells both in vivo and in vitro, and decreased Hoechst 33342 signals in vitro. cGAS, STING, p-TBK1, p-IRF3, and NF-κB expressions were up-regulated both in vivo and in vitro respectively and the up-regulated indexes were reversed by naringin. Transfection of cGAS-siRNA and cGAS-cDNA significantly down-regulated and up-regulated cGAS-STING signaling-related protein expressions, respectively, and partially weakened naringin-induced amelioration on these indexes, suggesting that deactivation of cGAS-STING signaling is the crucial target for naringin-induced amelioration on I/R-injured intestine.

Effects of liposoluble components of highland barley spent grains on physiological indexes, intestinal microorganisms, and the liver transcriptome in mice fed a high-fat diet.

The purpose of this study was to investigate the effects of the active ingredients of barley lees on the physiological indexes, intestinal flora, and liver transcriptome of mice fed a high-fat diet. Twenty-four male C57BL/6J mice were randomly divided into 4 groups and fed the experimental diets for 5 weeks. The results showed that the fat-soluble components of distillers' grains significantly reduced body weight, abdominal fat, perirenal fat, blood glucose, low-density lipoprotein cholesterol, triglycerides, and total cholesterol in the high-fat diet-fed mice (p < .05), significantly decreased alanine aminotransferase and malondialdehyde levels, and significantly increased total superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase levels (p < .05). At the phylum level, lipid-soluble components significantly increased the abundance of Bacteroidetes and decreased the Firmicutes/Bacteroidetes ratio. At the genus level, the relative abundances of Bacteroidetes and Clostridium were increased. Transcriptomic analysis showed that lipid-soluble components of spent grains reduced the mRNA expression of ANGPTL8, CD36, PLTP, and SOAT1 and increased the mRNA expression of CYP7A1 and ABCA1 in the cholesterol metabolism pathway, promoted the transport of cholesterol, and inhibited the absorption of cholesterol, which can decrease cholesterol levels by speeding up the conversion of cholesterol into bile acids.

Vitamin C as a potential ameliorating agent against hepatotoxicity among alcoholic abusers.

Drug and substance abuse remains a major medical problem globally. Alcohol consumption, particularly heavy drinking, is an important risk factor for many health problems and is a major contributor to the global burden of disease. Vitamin C has proven to be defensive against toxic substances and provides antioxidant and cytoprotective activity to hepatocytes. The aim of this study was to investigate vitamin C as a potential ameliorating agent against hepatotoxicity among alcohol abusers. This study was a cross-sectional study that included eighty male hospitalized alcohol abusers and twenty healthy people as a control group. Alcohol abusers received standard treatment plus vitamin C. Total protein, albumin, total Bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and 8-hydroxhguanosine (8-OHdG) were investigated. This study reported that, in the alcohol abuser group, there was a significant increase in the total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant decrease in albumin, GSH and CAT compared with the control group. The alcohol abuser group treated with vitamin C showed a significant decrease in total protein, bilirubin, AST, ALT, ALP, TBARS, SOD and 8-OHdG; on the other hand, there was a significant increase in albumin, GSH and CAT compared with the control group. This study's findings suggest that alcohol abuse induces significant alterations in various hepatic biochemical parameters and oxidative stress and that vitamin C has a partial protective role in countering alcohol abuse-induced hepatotoxicity. Using vitamin C as an adjunctive supplement to standard treatment may be helpful in minimizing the toxic side effects of alcohol abuse.

Non-alkolik yağlı karaciğer hastalığında kafein alımı ve karaciğer biyobelirteçleri arasındaki ilişki

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in developed countries. The aim of this study is to examine the effects of caffeine intake on some parameters of liver metabolism in individuals with NAFLD.&#x0D; Materials and Methods: A total of 20 female and 20 male subjects between the ages of 19 to 64, who were diagnosed with NAFLD, were included in the study. To determine caffeine intake, a specially developed caffeine-food frequency questionnaire was administered by a trained dietitian. Individuals were categorized into 3 groups according to their caffeine intake; Group 1: ≤150 mg/day, Group 2: 150-250 mg/day, and Group 3: ≥250 mg/day. Anthropometric measurements and biochemical parameters were recorded. Protein quantities in serum samples were determined by ELISA method.&#x0D; Results: The body fat composition of group 1 was higher than group 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of group 3 were higher than group 1 and group 2, respectively. High-density lipoprotein cholesterol (HDL-C) level of group 3 was lower than group 1 and group 2. There was a positive correlation between total caffeine intake and ALT level. There was no significant difference between the caffeine intake groups in terms of serum protein levels. In addition, there was not found significant correlation between serum protein levels and total caffeine intake.&#x0D; Conclusion: Caffeine intake of ≥250 mg/day may increase ALT and AST levels and decrease HDL-C level in individuals with NAFLD.

Mediterranean Diet Improves Plasma Biomarkers Related to Oxidative Stress and Inflammatory Process in Patients with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40-60 years old) diagnosed with NAFLD. Anthropometric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620.

Effects of dietary pomegranate peel supplementation on growth performance and biochemical responses of common carp, Cyprinus carpio, to chronic crowding stress

In the present study, the effects of dietary pomegranate peel (PP) at 0 (PP0; control), 5 (PP5), 10 (PP10), 15 (PP15), and 20 (PP20) g/kg were investigated in common carp, Cyprinus carpio (18.1 ± 0.42 g), under normal and stressful conditions. The fish were fed the aforementioned diets over two 4-week periods, one under normal stocking density (5 g/L; basal) and the other under high stocking density (15.5–16.3 g/L; stressed). The results showed that there were no significant differences in growth performance between the PP0 and PP5 treatments. However, PP10, PP15, and PP20 showed deteriorated growth performance, compared to PP0 treatment. The poorest growth parameters have been observed in PP15 and PP20 treatments. Plasma cortisol, glucose, alanine aminotransferase, and aspartate aminotransferase significantly increased after the stress in all treatments. PP5 and PP10 had significantly lower plasma cortisol and PP10 and PP15 had significantly lower plasma glucose and aspartate aminotransferase, compared to PP0 treatment. Increase in dietary PP levels significantly decreased alanine aminotransferase activity. The stress and increase in dietary PP levels significantly decreased the plasma T3 and T4 levels. Dietary PP significantly improved plasma lysozyme (PP5, PP10, and PP15) and complement (PP5 and PP10) activities and mitigated their decrease after the stress (the best effects in PP10), but was not beneficial in mitigating plasma total immunoglobulin decrease after the stress. Dietary PP (5–15 g/kg) significantly decreased hepatic antioxidant enzymes activities and mitigated their elevations after the stress. Hepatic malondialdehyde significantly decreased by dietary PP administration, but increased after the stress. The lowest hepatic malondialdehyde level was observed in PP10 treatment. In conclusion, dietary 5 g/kg PP is recommended as the best supplemental level that improves the fish health, without adverse effects on the fish growth performance.

Dietary docosahexaenoic acid reduces fat deposition and alleviates liver damage induced by D-galactosamine and lipopolysaccharides in Nile tilapia (Oreochromis niloticus)

Liver health is important to maintain survival and growth of fish. Currently, the role of dietary docosahexaenoic acid (DHA) in improving fish liver health is largely unknown. This study investigated the role of DHA supplementation in fat deposition and liver damage caused by D-galactosamine (D-GalN) and lipopolysaccharides (LPS) in Nile tilapia (Oreochromis niloticus). Four diets were formulated as control diet (Con), Con supplemented with 1 % DHA, 2 % DHA and 4 % DHA diets, respectively. The diets were fed to 25 Nile tilapia (2.0 ± 0.1 g, average initial weight) in triplicates for four weeks. After the four weeks, 20 fish in each treatment were randomly selected and injected with a mixture of 500 mg D-GalN and 10 μL LPS per mL to induce acute liver injury. The results showed that the Nile tilapia fed on DHA diets decreased visceral somatic index, liver lipid content and serum and liver triglyceride concentrations than those fed on the Con diet. Moreover, after D-GalN/LPS injection, the fish fed on DHA diets decreased alanine aminotransferase and aspartate transaminase activities in the serum. The results of liver qPCR and transcriptomics assays together showed that the DHA diets feeding improved liver health by downregulating the expression of the genes related to toll-like receptor 4 (TLR4) signaling pathway, inflammation and apoptosis. This study indicates that DHA supplementation in Nile tilapia alleviates the liver damage caused by D-GalN/LPS through increasing lipid catabolism, decreasing lipogenesis, TLR4 signaling pathway, inflammation, and apoptosis. Our study provides novel knowledge on the role of DHA in improving liver health in cultured aquatic animals for sustainable aquaculture.

Optimal dose of silymarin for the management of drug‑induced liver injury in oncology.

Systemic oncological treatment may cause drug-induced liver injury (DILI). Therefore, there is a pressing need for an active drug able to accelerate liver regeneration. Silymarin mitigates oxidative stress, and inhibits pro-inflammatory and pro-apoptotic cytokines and the fibrotic transformation of liver tissue. Currently, there are a lack of data regarding the optimal dosage of silymarin and its efficacy. Thus, the present retrospective study aimed to determine the optimal dose of silymarin for use in oncological DILI treatment. For this purpose, 180 patients with solid malignancies treated with systemic oncological therapy and silymarin between January, 2015 and November, 2021 were enrolled in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (Bil) levels, as well as the dose of silymarin were assessed at the initiation of silymarin treatment, after 3-6 weeks and after 6-12 weeks. Pearson's correlation analysis was performed to evaluate the correlation between the initial dose of silymarin (IDoS), and the ALT, AST and Bil levels. The effects of four independent variables, namely IDoS, the initial dose reduction of systemic treatment, the systemic treatment dose reduction at first assessment (DR1M) and the elevation of the silymarin dose at first control on the ALT, AST and Bil levels were evaluated using regression analysis. The median IDoS was 450 mg. A decrease in or the stabilization of the ALT, AST and Bil levels after 6-12 weeks were observed in 68.63, 65.85 and 53.25% of patients, respectively. There was a weak correlation between IDoS and the decrease in ALT and AST levels after 6-12 weeks (correlation coefficient, R=0.361 and 0.277 respectively, P<0.001). No significant correlation between the IDoS and a decrease in Bil levels was observed. DR1M was a negative predictor for a decrease in Bil levels in patients with liver tumors. On the whole, the present study demonstrates that silymarin appears to be efficient in alleviating DILI at a dose of 300-450 mg. A further increase in the dose of silymarin may not lead to an adequate increase in its efficacy.

A285 CHANGE IN ALT DURING MODIFIED OPTIFAST WEIGHT LOSS PROGRAM IN INDIVIDUALS AT RISK FOR NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract Background Obesity is linked to various health complications, including diabetes, metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent cause of abnormally high alanine aminotransferase (ALT) levels. ALT is released at higher levels during hepatocellular injury and represents a simple, low cost and non-invasive method of assessing liver damage. There are conflicting data on ALT response to weight loss between men and women, with some evidence of transient increase in ALT levels in women. Purpose The aim of this study was to assess the impact of a dietary weight loss intervention with Optifast on ALT in patients with obesity who have baseline elevated ALT levels. Method This was a retrospective cohort study of Ontario adults who participated in a 26 week weight loss program, including 6 or 12 weeks of low-calorie liquid diet meal replacement with Optifast 900® (Nestlé, Canada), between 1992 and 2015. We included patients with elevated baseline ALT levels, defined by &amp;gt; 40 U/L, who had at least one follow-up ALT between week 15 and 26. We excluded patients with nonadherence to dietary intervention, established liver disease or using hepatotoxic drugs, excessive alcohol intake (&amp;gt;11U/wk for females and &amp;gt;14U/wk for males), and insufficient data to calculate FIB-4. The primary outcome was change in ALT levels, measured by normalization (post-intervention ALT &amp;lt; 40 U/L), percentage decrease and absolute decrease. Multiple linear regressions were obtained for the relationship between ALT changes and age, sex, body mass index (BMI) and FIB-4. All analyses were conducted in SPSS. P value of ≤0.05 was considered statistically significant. Result(s) 444 patients met study criteria. Mean age was 47.1 years +/- 10.9, 49 % of patients were female, and mean BMI was 43.5 kg/m2 +/- 7.9. All patients lost weight, with mean weight loss 27.3 kg +/- 11.5 and a mean 20.7% decrease from baseline weight. Mean ALT at baseline was 58.9 U/L +/- 25.4 and mean ALT post intervention was 32.3 U/L +/- 28.1 (p &amp;lt;0.01). 85.1% of patients had normalization of ALT. Mean % decrease in ALT was 41.9% and mean absolute decrease in ALT was 26.6 U/L +/- 25.4. Younger age and higher baseline FIB-4 were significantly associated with a larger decrease in ALT levels, while sex and initial BMI were not significantly associated with changes in ALT. Conclusion(s) In patients with obesity and baseline elevated ALT, dietary weight loss intervention with Optifast leads to ALT normalization in most patients, regardless of sex. Younger age at baseline and higher baseline FIB-4 are significantly associated with greater decrease in ALT. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Elucidation of the role of α-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice.

Although methotrexate (MTX) is used to treat several malignancies and chronic inflammatory diseases, its clinical use is constrained because of its negative side effects, the most prevalent of which are hepatotoxicity and nephrotoxicity. So, this study aims to determine whether α-lipoic acid (ALA) and vitamin C can protect mice against the liver damage that methotrexate causes. A total of 49 male mice were divided into seven groups at random. Group I received sodium bicarbonate, while groups II to VII received an intraperitoneal injection of MTX (20 mg/kg) on the tenth day, following ten days of pretreatment with ALA (60 mg/Kg), ALA (120 mg/Kg), vitamin C (100 mg/Kg), vitamin C (200 mg/Kg), ALA (60 mg/Kg), and vitamin C (100 mg/kg). When compared to mice in group I, mice in group II (the control group) had significantly higher levels of the enzymes malondialdehyde (MDA), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significantly lower (p <0.05) levels of the enzymes superoxide dismutase (SOD) and glutathione (GSH). As compared to the control group, pretreatment groups with ALA and vitamin C showed a dose-dependent substantial rise (p <0.05) in GSH and SOD levels, a dose-dependent notable decrease (p <0.05) in MDA, ALT, ALP, and LDH levels, and better liver histological architecture. In order to increase the antioxidant capacity, pretreatment with ALA and vitamin C may be able to prevent MTX-induced hepatotoxicity. These results imply that ALA and vitamin C are useful in the treatment of MTX-induced liver damage.

Quercetin Application for Common Carp (Cyprinus carpio): I. Effects on Growth Performance, Humoral Immunity, Antioxidant Status, Immune-Related Genes, and Resistance against Heat Stress.

This study was done to evaluate the effect of different quercetin levels on growth performance, immune responses, antioxidant status, serum biochemical factors, and high-temperature stress responses in common carp (Cyprinus carpio). A total number of 216 common carp with an average weight of 27.21 ± 53 g were divided into 12 tanks (four treatments × three replications) and fed 0 mg/kg quercetin (T0), 200 mg/kg quercetin (T1), 400 mg/kg quercetin (T2), and 600 mg/kg quercetin (T3) for 60 days. There were significant differences in growth performance, and the highest final body weight (FBW), weight gain (WG), specific growth rate (SGR), and feed intake (FI) were observed in T2 and T3 (P < 0.05). Different quercetin levels significantly increased complement pathway activity (ACH50) and lysozyme activity both before and after heat stress (P < 0.05). Catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were significantly increased in fish exposed to heat stress, but fish fed with a supplemented diet with quercetin showed the lowest levels both before and after heat stress (P < 0.05). Superoxide dismutase (SOD) levels were significantly enhanced in fish fed diets supplemented with quercetin in both phases (P < 0.05). Different quercetin levels led to a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) before and after the challenging test (P < 0.05). Glucose and cortisol levels were significantly higher in the control group compared to the other treatments in both phases (P < 0.05). The expression of glutathione peroxidase (GPx) and lysozyme was markedly upregulated in fish fed with quercetin-supplemented diets (P < 0.05). No marked effects were observed for growth hormone (GR) and interleukin-8 (IL8) (P > 0.05). In conclusion, dietary quercetin supplementations (400-600 mg/kg quercetin) improved growth performance, immunity, and antioxidant status and increased tolerance to heat stress.

Self-Propelled Ultrasmall AuNPs-Tannic Acid Hybrid Nanozyme with ROS-Scavenging and Anti-Inflammatory Activity for Drug-Induced Liver Injury Alleviation.

Developing nanomedicines with superior reactive oxygen species (ROS) scavenging capability has emerged as a promising strategy in treating ROS-related diseases, for example, drug-induced liver injury. However, designing nanoscavengers with the self-propelling ability to scavenge ROS actively remains challenging. Here, a self-propelled silica-supported ultrasmall gold nanoparticles-tannic acid hybrid nanozyme (SAuPTB) is designed that can effectively alleviate acetaminophen (APAP)-induced liver injury by scavenging excessive ROS and regulating inflammation. SAuPTB exhibits multienzyme activity and displays significantly enhanced diffusion under hydrogen peroxide (H2 O2 ). This in vitro research shows that SAuPTB can effectively eliminate ROS, increasing the viability of H2 O2 -stimulated cells and reducing the cytotoxicity of APAP/H2 O2 -treated AML12 cells. The in vivo studiesshow that SAuPTB can accumulate at inflammatory sites in mouseliver, resulting in the decrease of alanine aminotransferase, aspartate aminotransferase, and ROS, reduction in pro-inflammatory cytokines and chemokines, hence reduced hepatocyte necrosis, liver injury, and mortality. Furthermore, SAuPTB activates the nuclear erythroid 2-related factor 2 pathway to upregulate antioxidative genes and reduce oxidative stress. Finally, the liver showsdecreased high mobility group box 1 and F4/80+ macrophages, suggesting an anti-inflammatory response. This work provides a novel design strategy of nanozymes for ROS-related disease treatment.

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity.

Human genome-wide association studies found single-nucleotide polymorphisms (SNPs) near LYPLAL1 (Lysophospholipase-like protein 1) that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease, we created and characterized a mouse knockout (KO) of Lyplal1. We fed the experimental group of mice a high-fat, high-sucrose (HFHS) diet for 23 weeks, and the controls were fed regular chow diet. Here, we show that CRISPR-Cas9 whole-body Lyplal1 KO mice fed an HFHS diet showed sex-specific differences in weight gain and fat accumulation as compared to chow diet. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, had white fat mass, and had adipocyte diameter not accounted for by changes in the metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and decreased alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.

Effect of nano-micelle curcumin on hepatic enzymes: A new treatment approach for non-alcoholic fatty liver disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes with no consumption of alcohol. Recently, curcumin is a natural polyphenol found in turmeric has been examined for the treatment of NAFLD. This study aimed to assess the efficacy of 160 mg/day nano-micelle curcumin on the amelioration of NAFLD by measuring liver enzymes. Patients with NAFLD were randomly divided into curcumin (intervention group n=33) and placebo (n=33) groups and at the end of the study, the data of 56 participants who completed the 2-month intervention were analyzed. Laboratory tests and questionnaires were used to gather information. Both groups received recommendations for lifestyle modification, and were advised to other necessary advices. Patients in the curcumin group received 160 mg/day of nano-micelle curcumin in two divided doses for 60 days. The 2 groups were followed up for two months and clinical and laboratory indices were compared. Our data showed a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the curcumin group (p<0.01) as well as a significant difference between the groups before and after the intervention in curcumin group (p<0.05). Interestingly, a meaningful decrease in AST serum level was observed in the intervention group (p<0.01). Our study demonstrated that short-term supplementation with nano-micelle curcumin results in the reduction of AST and ALT and is beneficial for the treatment of NAFLD.

Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial

The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10–90 μg) or placebo for 12 weeks. In Part C, 152 patients were randomized to receive tropifexor 140 µg, tropifexor 200 µg or placebo (1:1:1) for 48 weeks. The primary endpoints were safety and tolerability to end-of-study, and dose response on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic fat fraction (HFF) at week 12. Pruritus was the most common adverse event in all groups, with a higher frequency in the 140- and 200-µg tropifexor groups. Decreases from baseline in ALT and HFF were greater with tropifexor versus placebo at week 12, with a relative decrease in least squares mean from baseline observed with all tropifexor doses for ALT (tropifexor 10–90-μg dose groups ranged from −10.7 to −16.5 U l−1 versus placebo (−7.8 U l−1) and tropifexor 140- and 200-μg groups were −18.0 U l−1 and −23.0 U l−1, respectively, versus placebo (−8.3 U l−1)) and % HFF (tropifexor 10–90-μg dose groups ranged from −7.48% to −15.04% versus placebo (−6.19%) and tropifexor 140- and 200-μg groups were −19.07% and −39.41%, respectively, versus placebo (−10.77%)). Decreases in ALT and HFF were sustained up to week 48; however, similar trends in AST with tropifexor at week 12 were not observed. As with other FXR agonists, dose-related pruritus was frequently observed. Clinicaltrials.gov registration: NCT02855164

Treatment with Markhamia tomentosa Benth. K. Schum prevents carbon tetrachloride-induced liver damage in rats

Objective: Markhamia tomentosa (Bignoniaceae) is a medicinal plant with several pharmacological properties. However, its hepatoprotective effects have been little studied. The aim of this study was to evaluate the protective effects of the aqueous trunk bark extract of this plant against carbon tetrachloride (CCl4)-induced liver injury in rat. Material and Methods: Thirty male albino Wistar rats were divided into six groups (five each) with Groups 1, 2, 3, and 4 as negative (distilled water), normal (distilled water), positive (silymarin 25 mg/kg), and plant extract (50 mg/kg) controls, respectively. Groups 5 and 6 were used as test groups and were given plant extract (25 or 50 mg/kg, respectively). Rats were pretreated once a day for 14 days orally with different substances. CCl4 (0.5 mL/kg, i.p.) was administered on days 4 and 11 to all groups except Groups 1 and 4, to induce hepatitis. The rats were then sacrificed on day 15; liver functions and oxidative stress were assessed as well as histopathological changes. Results: M. tomentosa extract significantly and dose dependently decreased alanine aminotransferase, aspartate aminotransferase, gamma-glutamine aminotransferase, total bilirubin, total cholesterol, and malondialdehyde values while increasing catalase, and glutathione values compared to the CCl4-treated group. Histological findings showed a reduction in necrosis and inflammatory cell infiltration in the liver while the lumen of distal and proximal tubes was improved in the kidney by the plant extract. These results may be due to some of the major bioactives compounds found in the aqueous extract. Conclusion: These findings suggest that the aqueous extract of M. tomentosa may have liver protective effects through its antioxidant and anti-inflammatory mechanisms, supporting thereby its ethnomedicinal uses.

ALS-L1023 from Melissa officinalis Alleviates Liver Fibrosis in a Non-Alcoholic Fatty Liver Disease Model.

ALS-L1023 is an ingredient extracted from Melissa officinalis L. (Labiatae; lemon balm), which is known as a natural medicine that suppresses angiogenesis. Herein, we aimed to determine whether ALS-L1023 could alleviate liver fibrosis in the non-alcoholic fatty liver disease (NAFLD) model. C57BL/6 wild-type male mice (age, 6 weeks old) were fed a choline-deficient high-fat diet (CDHFD) for 10 weeks to induce NAFLD. For the next 10 weeks, two groups of mice received the test drug along with CDHFD. Two doses (a low dose, 800 mg/kg/day; and a high dose, 1200 mg/kg/day) of ALS-L1023 were selected and mixed with feed for administration. Obeticholic acid (OCA; 10 mg/kg/day) was used as the positive control. Biochemical analysis revealed that the ALS-L1023 low-dose group had significantly decreased alanine transaminase and aspartate transaminase. The area of fibrosis significantly decreased due to the administration of ALS-L1023, and the anti-fibrotic effect of ALS-L1023 was greater than that of OCA. RNA sequencing revealed that the responder group had lower expression of genes related to the hedgehog-signaling pathway than the non-responder group. ALS-L1023 may exert anti-fibrotic effects in the NAFLD model, suggesting that it may provide potential benefits for the treatment of liver fibrosis.

Whey protein positively alters inflammatory markers and metabolic parameters of overweight and obese adults

Introduction: The effects of prolonged consumption of whey protein on health are controversial. This study aimed to determine whether whey protein positively alters health parameters of overweight and obese adults. Methods: Randomised controlled trial was conducted. Fifty-eight participants, aged 30-50 years, were randomly allocated into four groups and supplemented with 50 g protein for eight weeks (group 1: plant-based protein (PBP), group 2: whey protein isolate (WPI) with cocoa powder, group 3: PBP with whey protein concentrate (WPC), and group 4: WPI with milk powder). Body composition and biochemical parameters (kidney and liver functions, inflammation, oxidative stress, and antioxidant capacity) were evaluated at pre-intervention and 8 weeks after intervention. Results: At Week 8, group 3 had lower diastolic blood pressure, waist circumference, visceral fat, and risk of insulin resistance (p&lt;0.05 for all). Group 2 had decreased levels of total cholesterol and low-density lipoprotein cholesterol (p&lt;0.05 for all). A drop in triglyceride was seen in group 4 (p=0.026). Whey protein decreased alanine aminotransferase level (p=0.028), while PBP increased aspartate aminotransferase level (p=0.034). PBP or WPI with milk powder increased blood urea nitrogen level (p&gt;0.05 for all). Interleukin-6 and lactoferrin levels fell in all groups (p&lt;0.05), while hs-CRP increased in the PBP group (p=0.043). Group 2 experienced increased antioxidant capacity. However, levels of oxidative stress markers were significantly decreased in the PBP group and WPI with milk powder group. Conclusion: Whey protein revealed positive effects on anthropometric parameters and biochemical markers of overweight and obese adults. Therefore, proper supplementation of whey protein can potentially promote health.

Application of hepatic lobe hyperplasia techniques in the treatment of advanced hepatic alveolar echinococcosis: a single-centre experience

BackgroundThis study was designed to investigate clinical efficiency and application indications of hepatic lobe hyperplasia techniques for advanced hepatic alveolar echinococcosis (AE) patients.MethodsA retrospective case series covering 19 advanced hepatic AE patients admitted to the First Affiliated Hospital of Xinjiang Medical University from September 2014 to December 2021 and undergoing hepatic lobe hyperplasia techniques due to insufficient remnant liver volume were analyzed. Changes of liver function, lesions volume, remnant liver volume, total liver volume before and after operation have been observed.ResultsAmong the patients, 15 underwent portal vein embolization (PVE). There was no statistical difference in total liver volume and lesions volume before and after PVE (P > 0.05). However, the remnant liver volume was significantly increased after PVE (P < 0.05). The median monthly increase rate in future liver remnant volume (FLRV) after PVE stood at 4.49% (IQR 3.55–7.06). Among the four patients undergoing two-stage hepatectomy (TSH), FLRV was larger than that before the first stage surgery, and the median monthly increase rate in FLRV after it stood at 3.34% (IQR 2.17–4.61). Despite no statistical difference in total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) in all patients with PVE, four patients who underwent TSH showed a decrease in ALT, AST and GGT. During the waiting process before the second stage operation, no serious complications occurred in all patients.ConclusionsFor patients suffering from advanced hepatic AE with insufficient FLRV, PVE and TSH are safe and feasible in promoting hepatic lobe hyperplasia.