Liver Enzyme Levels Research Articles

The effects of astaxanthin supplementation on liver enzyme levels.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

Smoke Signals: Unraveling the Link between Cigarette Smoking and Serum Liver Markers

Introduction: Cigarette smoking is a major cause of global mortality and morbidity. It exposes the body to many harmful substances, such as cytotoxic, carcinogenic and free radicals, that can damage various organs. This study aims to investigate the effects of different levels of tobacco exposure on liver tissue, by measuring some serum biochemical markers of liver function.
 Materials and Methods: The project conducted at T.N.M.C Mumbai from January to December 2021 involved 60 male participants (18–35 years old), divided into smokers (30) and non-smokers (30). Smokers had varying smoking durations (1-5 years). Excluded participants with diseases affecting liver enzymes. Groups were age-matched for analysis. Smokers defined as those smoking >20 cigarettes daily for >1 month. Collected 5.0 ml venous blood, processed in heparinized tubes, and centrifuged for plasma separation. Enzymes SGOT, SGPT, ALP, Total Bilirubin, Direct Bilirubin were measured, and statistical analysis revealed significant differences.
 Results: In the study, age comparison between smokers and non-smokers showed no significant difference (p = 0.71). However, smokers exhibited significantly higher mean serum concentrations of SGOT and SGPT compared to non-smokers (p = 0.002 and p < 0.0001, respectively). Smokers also had elevated levels of ALP and total bilirubin with mean differences of 16.3 IU/L and 0.392 mg/dl, supported by 95% confidence intervals (6.72, 26.18) and (0.28, 0.504) and p values of 0.003 and 0.0004, respectively. No significant difference was observed in direct bilirubin levels (mean difference: 0.084 mg/dl, 95% CI: 0.065, 0.103, p = 0.191)
 Conclusion: In summary, the study suggests a correlation between smoking and elevated serum levels of liver enzymes and damage markers, indicating a potential adverse impact on liver function and increased susceptibility to liver diseases.

Impact of pemafibrate on lipid profile and insulin resistance in hypertriglyceridemic patients with coronary artery disease and metabolic syndrome.

This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male. Forty-one of 55 male patients were found to have MetS. In this sub-analysis, male patients with MetS (MetS group, n = 41) and those without MetS (non-MetS group, n = 14) were compared. The primary endpoint was a change in fasting serum triglyceride (TG) levels during pemafibrate therapy, and the secondary endpoints were changes in insulin resistance-related markers and liver function parameters. Serum TG levels significantly decreased (MetS group, from 266.6 to 148.0mg/dL, p < 0.001; non-MetS group, from 203.9 to 97.6mg/dL, p < 0.001); however, a percent change (%Change) was not significantly different between the groups (- 44.1% vs. - 51.6%, p = 0.084). Serum insulin levels and homeostasis model assessment of insulin resistance significantly decreased in the MetS group but not in the non-MetS group. %Change in liver enzyme levels was markedly decreased in the MetS group compared with that in the non-MetS group (alanine aminotransferase, - 25.1% vs. - 11.3%, p = 0.027; gamma-glutamyl transferase, - 45.8% vs. - 36.2%, p = 0.020). In conclusion, pemafibrate can effectively decrease TG levels in patients with MetS, and it may be a more efficient drug for improving insulin resistance and liver function in such patients.

Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial

BackgroundThe effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. Hypothesis/PurposeThis study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. Study designA total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. ResultsBoth QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (β, −0.128 [95 % CI, −0.25, −0.005], p = 0.041), aspartate transaminase (β, −0.134 [95 % CI, −0.256 to −0.012], p = 0.032), and fibrosis-4 score (β, −0.129 [95 % CI, −0.254 to −0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. ConclusionOur results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

Association between liver enzymes and type 2 diabetes: a real-world study.

This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.

Expression of miR-34a in Children with Progressive Familial Intrahepatic Cholestasis: A Cross-Sectional Study Based on Shiraz Pediatric Liver Cirrhosis Cohort Study

Background: Progressive familial intrahepatic cholestasis (PFIC) is a rare progressive liver disease associated with portal hypertension leading to liver failure. Most PFIC patients ultimately need liver transplantation. Therefore, identifying a precise, non-invasive biomarker for PFIC is very important. Objectives: This study aimed to investigate the microRNA-34a (miR-34a) expression levels in PFIC patients. Methods: A total of 18 PFIC patients were randomly selected from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), and 18 healthy subjects were enrolled in this study. Blood samples were obtained, and the gene expression of serum miR-34a was analyzed. Results: The results of this study showed that the serum level of miR-34a was significantly increased in PFIC patients, compared to the healthy group (P = 0.0327). However, no association was observed between miR-34a expression and clinical and laboratory findings of PFIC cases. Additionally, the results showed no correlation between miR-34a and serum levels of liver enzymes, albumin, gamma-glutamyl transpeptidase (GGT), and international normalized ratio (INR) among PFIC patients. Conclusions: miR-34a might be a beneficial, non-invasive target for PFIC diagnosis; however, further investigations with a larger population and longer duration are necessary to determine the potential of miR-34a as a diagnostic and therapeutic biomarker for PFIC.

2,3,5,4′- tetrahydroxystilbene-2-O-β-D- glucopyranoside (TSG)-Driven immune response in the hepatotoxicity of Polygonum multiflorum

Ethnopharmacological relevance2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) as the primary constituent of Polygonum multiflorum Thumb. (PM) possesses anti-oxidative, antihypercholesterolemic, anti-tumor and many more biological activities. The root of PM has been used as a tonic medicine for thousands of years. However, cases of PM-induced liver injury are occasionally reported, and considered to be related to the host immune status. Aim of the studyThe primary toxic elements and specific mechanisms PM causing liver damage are still not thoroughly clear. Our study aimed to investigate the influences of TSG on the immune response in idiosyncratic hepatotoxicity of PM. Materials and methodsThe male C57BL/6 mice were treated with different doses of TSG and the alterations in liver histology, serum liver enzyme levels, proportions of T cells and cytokines secretion were evaluated by hematoxylin and eosin (HE), RNA sequencing, quantitative real time polymerase chain reaction (qRT-PCR), Flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA), respectively. Then, primary spleen cells from drug-naive mice were isolated and cultured with TSG in vitro. T cell subsets proliferation and cytokines secretion after treated with TSG were assessed by CCK8, FCM and ELISA. In addition, mice were pre-treated with anti-CD25 for depleting regulatory T cells (Tregs), and then administered with TSG. Liver functions and immunological alterations were analyzed to evaluate liver injury. ResultsData showed that TSG induced liver damage, and immune cells infiltration in the liver tissues. FCM results showed that TSG could activate CD4+T and CD8+T in the liver. Results further confirmed that TSG notably up-regulated the levels of inflammatory cytokines including TNF-α, IFN-γ, IL-18, perforin and granzyme B in the liver tissues. Furthermore, based on transcriptomics profiles, some immune system-related pathways including leukocyte activation involved in inflammatory response, leukocyte cell-cell adhesion, regulation of interleukin-1 beta production, mononuclear cell migration, antigen processing and presentation were altered in TSG treated mice. CD8+T/CD4+T cells were also stimulated by TSG in vitro. Interestingly, increased proportion of Tregs was observed after TSG treatment in vitro and in vivo. Foxp3 and TGF-β1 mRNA expressions were up-regulated in the liver tissues. Depletion of Tregs moderately enhanced TSG induced the secretion of inflammatory cytokines in serum. ConclusionsOur findings showed that TSG could trigger CD4+T and CD8+T cells proliferation, promote cytokines secretion, which revealed that adaptive immune response associated with the mild liver injury cause by TSG administration. Regulatory T cells (Tregs) mainly sustain immunological tolerance, and in this study, the progression of TSG induced liver injury was limited by Tregs. The results of our investigations allow us to preliminarily understand the mechanisms of PM related idiosyncratic hepatotoxicity.

The effect of minor thalassemia on the liver function and lipid profile compared with major thalassemia.

It is thought that only patients with major thalassemia need to be under healthy control compared to minor. Thus, the aim of this work is to investigate the minor thalassemia complications in the liver status and compare them with the major thalassemia. So, 84 patients with thalassemia were randomly selected; 56 with major and 28 with minor. The Blood Samples were collected and used to determine the levels of ferritin, liver enzymes and lipid profiles. The results were showed that while there were no significantly differences in the ALP levels, ALT and AST levels were significantly higher in the major thalassemia compared to minor. All the patients with major and minor had abnormal higher ALP, 45% of major had abnormal higher AST and 30% of the major had abnormal ALT than normal range. Bild, BilT, cholesterol and trig levels were significantly higher while LDH and UHDL levels were significantly lower in the major compared to minor. The Bild levels in 90% of the major compared to 40% of the minor were abnormal higher than normal range. As conclusion, there were abnormality in the ALP and some lipid profile of minor thalassemia. So, the patients with minor thalassemia could be under risk of liver disorder so they need to be under control and to find the exact reason of this disorder need more researches.

A228 RISANKIZUMAB - DRUG INDUCED LIVER INJURY; A CASE REPORT

Abstract Background Risankizumab is a humanized monoclonal antibody to IL-23. It was initially used in the treatment of plaque psoriasis with recent approval to extend use to treat moderate to severe Crohn’s disease with evidence of endoscopic healing and clinical remission of disease. In the drugs safety manual, it has been reported to have transient liver enzyme elevation that is asymptomatic and not to a degree requiring drug discontinuation. No reported data on steatohepatitis. In this article we describe a 28 year old female, who had no evidence of liver disease in the past who underwent treatment with Risankizumab and within several months developed evidence of steatohepatitis with radiological evidence of significant hepatomegaly. Aims Case report details Drug induced liver injury to Risankizumab. Methods Case Report Results Drug induced liver injury with elevated liver enzyme levels and liver biopsy showing drug related liver changes likely in the setting of Risankizumab use. Conclusions Risankizumab is a newly approved drug in the setting of Crohn's disease, although described in the drug assessment report that it may cause transient hepatitis or eleveted liver enzymes in the setting of lower drug dose for Psoriasis use, the higher drug level used in the setting of Crohn's disease has not been formally evaluated and no previous known case reports of Drug induced Liver Injury to Risankizumab causing severe steatohepatitis Funding Agencies None

Effects of High-Dose Vitamin C on Liver Function, Systemic Inflammatory and Immune Responses in Patients with Severe Acute Pancreatitis

The objective of this study was to explore the impact of high-dose vitamin C on severe acute pancreatitis patients. This study involved 76 hospital patients from November 2022 to November 2023, divided into two groups: a high-dose group (44 patients) receiving 10 g of vitamin C daily and a routine-dose group (32 patients) receiving 1 g daily. The study evaluated treatment effects, liver function, inflammation levels, and blood T-lymphocyte subsets and complications. At 14 days, the high-dose group showed better overall treatment effects, lower levels of liver enzymes and inflammatory markers, and higher levels of T lymphocytes, with no significant difference in complications compared to the routine-dose group. The findings suggest that high-dose vitamin C effectively improves liver function, reduces inflammation, and boosts immunity in severe acute pancreatitis patients.

Primary hypoaldosteronism in a dog with concurrent suspected chronic hepatitis

A 3-year-old female spayed English Cocker Spaniel presented with a 2-month history of lethargy. The owner reported a single tonic-clonic seizure 7 months before presentation and intermittent mild gastrointestinal signs for the past 18 months. Initial investigations revealed hyponatraemia, hyperkalaemia and increased levels of liver enzymes. An adrenocorticotropic hormone stimulation test excluded hypocortisolism. The gastrointestinal signs resolved following a dietary change, suggesting that chronic enteropathy and most primary and secondary causes of hepatic disease were excluded, leaving idiopathic chronic hepatitis as the most likely cause of increased levels of liver enzymes. Liver parameters reduced to levels just above reference range after immunosuppressive doses of prednisolone. Aldosterone levels pre- and post-adrenocorticotrophic hormone stimulation were &lt;20 pmol/litre, consistent with mineralocorticoid deficiency. The mineralocorticoid deficiency was treated with desoxycorticosterone pivalate at 1–1.3 mg/kg subcutaneously every 48–87 days, which resulted in immediate and complete resolution of the clinical signs and electrolyte imbalance. Given the dog's signalment and results from clinical investigations, the isolated hypoaldosteronism is speculated to be caused by immune-mediated adrenal gland destruction. Isolated hypoaldosteronism should be considered a differential diagnosis for hyponatraemia in dogs, when an adrenocorticotrophic hormone stimulation test excludes hypocortisolism.

Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model

Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model. In vitro testing on primary hepatocytes demonstrated that Hsd17b13 ASO exhibited strong efficacy and specificity for knockdown of the Hsd17b13 gene. In choline-deficient, L-amino acid-defined, HFD (CDAHFD)-induced steatotic and fibrotic mice, therapeutic administration of Hsd17b13 ASO resulted in a significant and dose-dependent reduction of hepatic Hsd17b13 gene expression. The CDAHFD group exhibited considerably elevated liver enzyme levels, hepatic steatosis score, hepatic fibrosis, and increased fibrotic and inflammatory gene expression, indicating an advanced NASH-like hepatic fibrosis phenotype. Although Hsd17b13 ASO therapy significantly affected hepatic steatosis, it had no effect on hepatic fibrosis. Our findings demonstrate, for the first time, that Hsd17b13 ASO effectively suppressed Hsd17b13 gene expression both in vitro and in vivo, and had a modulatory effect on hepatic steatosis in mice, but did not affect fibrosis in the CDAHFD mouse model of NASH.

Effects of Extracellular Calcium Concentration on Hepatic Ischemia-Reperfusion Injury in a Rat Model.

Hypocalcemia is frequently identified during liver transplant. However, supplementation of extracellular calcium could induce increased intracellular calcium concentration, as a potential factor for injury to the liver graft. We evaluated the effects of regulating extracellular calcium concentrations on hepatic ischemia-reperfusion injury. We randomly divided 24 Sprague-Dawley rats into 3 groups: group C received normal saline (n = 8), group L received citrate to induce hypocalcemia (n = 8), and group L-Co received citrate followed by calcium gluconate to ameliorate hypocalcemia (n = 8). Liver enzyme levels and extracellular calcium were measured before surgery, 1 hour after ischemia, and 2 hours after reperfusion. The primary outcome was liver enzyme levels measured 2 hours after reperfusion. In addition, we evaluated intracellular calcium levels, lactate dehydrogenase activity, and histopathological results in liver tissue. Three groups demonstrated significant differences in extracellular calcium concentrations, but intracellular calcium concentrations in liver tissue were not significantly different. Group L showed significantly lower mean arterial pressure than other groups at 1 hour after ischemia (93.6 ± 20.8 vs 69.4 ± 14.2 vs 86.6 ± 10.4 mmHg; P = .02, for group C vs L vs L-Co, respectively). At 2 hours after reperfusion, group L showed significantly higher liver enzymes than other groups (aspartate aminotransferase 443.0 ± 353.2 vs 952.3 ± 94.8 vs 502.4 ± 327.3 U/L, P = .01; and alanine aminotransferase 407.9 ± 406.5 vs 860.6 ± 210.9 vs 333.9 ± 304.2 U/L, P = .02; for group C vs L vs L-Co, respectively). However, no significant difference was shown in lactate dehydrogenase and histological liver injury grade. Administering calcium to rats with hypocalcemia did not increase intracellular calcium accumulation but instead resulted in less hepatic injury compared with rats with low extracellular calcium concentrations in this rat model study.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats

BackgroundMelissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation.MethodsHyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined.ResultsMO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes’ activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway.ConclusionAccordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

Phytolacca Dodecandra (L' Herit) (Phytolaccaceae) Methanol Root Extract Protects Liver from Acetaminophen-Induced Injury in Rats.

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury.

Alcoholic Hepatitis

Alcoholic hepatitis is a serious liver condition characterized by inflammation and liver damage caused by excessive alcohol consumption. This condition represents a significant health concern worldwide as it can progress to more severe liver diseases, including cirrhosis and liver failure. This abstract provides an overview of alcoholic hepatitis, including its causes, symptoms, diagnosis, and treatment. Long-term alcohol consumption is the primary cause of alcoholic hepatitis. When alcohol is metabolized in the liver, it generates toxic byproducts that can lead to inflammation and cellular damage. Over time, repeated episodes of damage can result in alcoholic hepatitis. Patients with this condition may present with various symptoms including jaundice, abdominal pain, nausea, vomiting, fever, and an enlarged liver. Diagnosis of alcoholic hepatitis typically involves a combination of medical history assessment, physical examination, blood tests, and imaging studies. Elevated levels of liver enzymes, such as AST and ALT, are common laboratory findings. A liver biopsy may be required to confirm the diagnosis and assess the extent of liver damage. Treatment of alcoholic hepatitis primarily focuses on alcohol cessation, which is essential to prevent further liver damage and improve the chances of recovery. Supportive care, such as nutritional supplementation and the management of complications, is also essential. Hospitalization may be necessary for severe cases. The prognosis varies depending on the severity of the condition and the patient's response to treatment. Complete abstinence from alcohol significantly improves the chances of recovery; however, some individuals may progress to advanced liver disease or even liver failure. Liver transplantation may be considered for those with end-stage liver disease. key words Alcoholic hepatitis Liver inflammation Excessive alcohol consumption Liver damage Cirrhosis Liver failure Symptoms Jaundice Abdominal pain Nausea Vomiting Fever Enlarged liver Diagnosis Liver enzymes AST (Aspartate Aminotransferase) ALT (Alanine Aminotransferase) Liver biopsy Treatment Alcohol cessation.

Effects of prazosin treatment on liver enzymes are moderated by alcohol withdrawal symptoms in individuals with alcohol use disorder.

Alcohol use disorder (AUD) is associated with significant liver pathology marked by elevated liver enzymes. Prazosin, an alpha1-noradrenergic antagonist significantly improves alcohol drinking outcomes in individuals with alcohol withdrawal symptoms (AW), but effects on liver enzymes are unknown. We assessed the effects of prazosin treatment on the liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), and gamma-glutamyltransferase (GGT) in individuals with AUD. Participants (N=100) with AUD were enrolled in a 12-week randomized controlled trial and received either placebo or 16 mg/day of prazosin. Whole blood was drawn from 92 participants to measure liver enzyme levels every 4 weeks, and severity of AW was assessed weekly. Analysis predicting liver function outcomes used linear mixed effects models. Controlling for alcohol consumption, a significant AW × treatment effect was seen for ALT (p < 0.05), AST (p < 0.05) and GGT (p < 0.01). Additionally, AST (b = 0.2, p < 0.01), ALT (b = 0.2, p < 0.05), and GGT (b = 0.3, p < 0.01) were elevated in individuals with higher AW in the placebo but not in the prazosin group (AST: p > 0.66; ALT: p > 0.65). Only in the prazosin group were lower GGT levels associated with higher withdrawal severity (b = -0.16, p < 0.05). We found an interaction of alcohol withdrawal symptoms and prazosin treatment on liver enzyme levels, which were not influenced by week in the trial or the amount of alcohol consumed. Together, these findings suggest that prazosin treatment reduces liver enzymes over the course of AUD treatment among individuals with significant AW, though replication to establish clinical utility is needed.

Mitochondrial-mediated apoptosis as a therapeutic target for FNC (2′-deoxy-2′-b-fluoro-4′-azidocytidine)-induced inhibition of Dalton’s lymphoma growth and proliferation

PurposeT-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2′-deoxy-2′-β-fluoro-4′-azidocytidine (FNC), against T-cell lymphoma using Dalton’s lymphoma (DL)-bearing mice as a model.MethodsBalb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations.ResultsThe results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects.ConclusionFNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC’s proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC’s potential role in designing a better therapeutic approach against NHL.

Evaluation of the Effect of Cichorium intybus L. on the Liver Enzymes in Burn Patients: A Randomized Double-Blind Clinical Trial.

Burn injuries are considered an important public health problem in the world. Burns are considered the fourth most common kind of trauma in the world, after traffic accidents, falls, and interpersonal violence. Various biochemical agents are involved in the burn healing process such as cytokines (such as IL-6 and TNF-α), antioxidants, and liver and kidney damage biomarkers. Cichorium intybus L. and milk thistle extracts showed a wide range of pharmacological activities such as significant antimicrobial effect and antioxidant activity, as well as anti-inflammatory, antidiabetic, antiproliferative, antiprotozoal, and hepatoprotective effect. Also, these two herbs possess blood-cleansing, detoxifying, laxative, and invigorating activities. Some research confirmed that the preparations of the extract are very suitable for the treatment of nonalcoholic fatty liver disease. This is a double-blind randomized controlled clinical trial. Patients with 2nd and 3rd degree burns have been selected to participate in the study according to the inclusion criteria. A total of 60 patients were selected and divided into intervention and control groups (30 patients in each group). Patients in the intervention group received chicory seed syrup 10 cc three times a day and 1 placebo capsule, and those in the control group received placebo syrup (10 cc three times a day) and one Livergol (140 mg of silymarin in each capsule) capsule. Lab data such as liver function tests, albumin, creatinine, BUN, and hemoglobin were checked every 3 days and 1 week after discharge. The treatment lasted for 4 weeks. According to the results of the study, although the average of liver enzymes at the end of the study does not show a significant difference between the two groups, the level of liver enzymes in each group decreased on the 15th day of the study compared to the first day. This trial is registered with IRCT20180609040016N1.

THE PROTECTIVE EFFECT OF DEXMEDETOMIDINE ON THE LIVER INJURY IN SEPSIS THROUGH INHIBITION OF NECROPTOSIS.

Background: Sepsis-induced liver injury leads to extensive necroptosis in hepatocytes, which is the main factor of liver dysfunction. This study aims to investigate the protective effect of dexmedetomidine (DEX) on septic liver and to explore whether its molecular mechanism is related to the modulation of necroptosis. Methods: The model of septic liver injury was induced by cecal ligation and puncture (CLP) in rats. DEX and necrostatin-1(Nec-1), a specific antagonist of necroptosis, were administered 1 h before CLP. The levels of arterial blood gas, serum aspartate aminotransferase, and alanine aminotransferase were measured at 6, 12 and 24 h after CLP. The survival rate was observed 24 h after CLP. Liver pathological changes and apoptosis, the contents of IL-6 and TNF-α in liver tissue homogenates, the ROS content in liver tissue, and the expression levels of RIP1, RIP3, MLKL, and HMGB1 were detected. Results: At 6, 12, and 24 h after CLP, the levels of aspartate aminotransferase, and alanine aminotransferase levels increased, and liver enzyme levels gradually increased with the progression of sepsis. In arterial blood gas analysis, P a O 2 gradually decreased and lactic acid concentration gradually increased during these three periods. The morphological impairment of liver tissues, increased apoptosis, elevated inflammatory factors (IL-6 and TNF-α), increased ROS level, and necroptosis components (RIP1, RIP3, MLKL, and HMGB1) were all observed in sepsis rats. However, these injuries can be ameliorated by pretreatment with DEX. Meanwhile, Nec-1 pretreatment also reduced the expression of RIP1, RIP3, MLKL, HMGB1, and ROS level. Conclusion: Our study suggests that DEX alleviates septic liver injury, and the mechanism is associated with the inhibition of necroptosis.