Elevated Liver Enzyme Levels Research Articles

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

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

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

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

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

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

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection

BackgroundRespiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.MethodsIn a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo.ResultsThe intention-to-treat population included 244 participants, and the safety population included 302. The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater with ziresovir than with placebo (−3.4 points [95% confidence interval {CI}, −3.7 to −3.1] vs. −2.7 points [95% CI, −3.1 to −2.2]; difference, −0.8 points [95% CI, −1.3 to −0.3]; P=0.002). The reduction in the RSV viral load at day 5 was greater in the ziresovir group than in the placebo group (−2.5 vs. −1.9 log10 copies per milliliter; difference, −0.6 log10 copies per milliliter [95% CI, −1.1 to −0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16% with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%). Resistance-associated mutations were identified in 15 participants (9%) in the ziresovir group.ConclusionsZiresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. (Funded by Shanghai Ark Biopharmaceutical; AIRFLO ClinicalTrials.gov number, NCT04231968.)

Contrast-enhanced ultrasound-guided percutaneous transhepatic cholangiodrainage is a safe and effective procedure for patients with malignant biliary obstruction and stage 3 chronic kidney disease

ObjectivesThis study aimed to validate the efficacy and safety of contrast-enhanced ultrasound-guided percutaneous transhepatic cholangiodrainage (CEUS-PTCD) as a biliary drainage procedure in patients with malignant biliary obstruction and stage 3 chronic kidney disease (CKD3). Materials and methodsBetween January 2019 and December 2023, 634 patients who underwent CEUS-PTCD were retrospectively enrolled in this study. During the procedure, imaging parameters such as the maximum diameter of the dilated bile duct, presence of ascites, detailed findings from CEUS, and clinical outcomes were meticulously recorded. Laboratory results, including serum bilirubin levels, liver function tests, and estimated glomerular filtration rate (eGFR), were evaluated in one day before and three days after procedure. The aforementioned parameters were compared using the paired-sample t test and the Wilcoxon test. ResultsA total of 66 (10.41 %) patients with malignant biliary obstruction and CKD3 were included in the final analysis (median age: 66, range: 30–89 years, 46 males and 20 females). Procedure records indicated that 23 patients (34.8 %) had a maximum biliary duct dilation diameter of ≤ 4 mm, while 5 patients (7.6 %) exhibited mild ascites. Additionally, 24 patients (36.4 %) had ultrasound contrast agent entry into both the biliary duct and bloodstream. All patients successfully achieved external bile drainage following CEUS-PTCD, with no significant complications observed during or after the intervention. Post-procedure, there was a statistically significant reduction in all previously elevated serum bilirubin and liver enzyme levels (P-values were less than 0.05). Furthermore, no statistically significant alterations in eGFR were observed prior to or following CEUS-PTCD across all patients (P = 0.295), including comparisons between groups with and without the ultrasound contrast agent into the bloodstream (P = 0.254). ConclusionCEUS-PTCD is a safe and effective biliary drainage procedure for patients with malignant biliary obstruction and CKD3.

Ursodeoxycholic acid in hepatobiliary diseases

Background: This study aimed to summarize evidence of ursodeoxycholic acid (UDCA) use in the management of hepatobiliary diseases, present indications for UDCA use in Korea, and reimbursement criteria for UDCA use in the country.Current Concepts: UDCA is currently approved for the treatment and prevention of gallstone in obese patients with rapid weight loss after post-bariatric surgery, primary biliary cirrhosis (PBC), chronic liver disease with markedly elevated liver function test values, and chronic hepatitis C. However, the approval and reimbursement criteria for UDCA depend on the dose, specific diseases, and circumstances. UDCA is administered at doses of 100, 200, and 300 mg. The 100 mg dose is available over-the-counter, whereas a prescription is required for the 200 and 300 mg doses. The approval standards differed by dose: UDCA 100 mg for biliary diseases and chronic liver disease; UDCA 200 mg for gallstone, PBC, and chronic hepatitis C; and UDCA 300 mg for PBC, gallstone prevention in obese patients, and patients who had undergone gastrectomy. Co-administration of UDCA with antiviral drugs may require patients to bear some costs. UDCA can be combined with either milk thistle or biphenyl dimethyl dicarboxylate but not both.Discussion and Conclusion: UDCA is a relatively safe medication with many benefits. The current reimbursement standards for hepatobiliary diseases include chronic liver disease with elevated liver enzyme levels, gallstone, PBC, chronic hepatitis B, and chronic hepatitis C. Because UDCA is administered at varied doses, it is important to know the appropriate dose and regimen for each condition.

Acute Liver Injury and Bilateral Pulmonary Artery Thrombosis Due to Hypereosinophilic Syndrome.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Cascara kombucha potential as a functional food for fasting glucose regulation, cholesterol control, and liver function modulation: in vitro and in vivo study

SummaryUnhealthy dietary patterns are a major contributor to obesity worldwide, leading to various adverse metabolic effects such as elevated liver enzyme levels and increased cholesterol concentrations. This study investigates the potential of cascara kombucha as a functional beverage to provide health benefits in both in vitro and in vivo models. Our results indicate that kombucha fermentation enhances the bioactive compounds in cascara, including polyphenols and flavonoids. The in vitro study found that cascara kombucha effectively decreased free radicals (DPPH and ABTS) levels, α‐amylase, and lipase activity, suggesting its potential to act as an antioxidant and modulate carbohydrate and lipid metabolism. In a mouse model, oral administration of cascara kombucha at a dose of 300 mg/kg body weight for 28 days successfully decreased fasting blood glucose levels, improved liver health by reducing aspartate transaminase and alanine transaminase levels, and lowered serum cholesterol content induced by a fat‐enriched diet compared to the untreated group. The levels of superoxide dismutase and catalase, suppressed by the fat‐enriched diet, were restored to normal. Additionally, cascara kombucha downregulated genes associated with inflammation induced by a fat‐enriched diet, including tnf‐α, IL‐6, IL‐1β, and cox‐2. It also positively affected the balance of intestinal microflora in mice by reducing coliform density and enhancing probiotic populations. These findings highlight the potential of cascara kombucha as a promising approach to addressing health issues caused by poor dietary habits and metabolic imbalances.

Novel microwave assisted carboxymethyl-graphene oxide and its hepatoprotective activity

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm−1 (COONa vibrations) and increased CH2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl4). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl4-induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury.Graphical abstract

Tranilast Inhibits TRPV2 and Suppresses Fibrosis Progression and Weight Gain in a NASH Model Mouse.

This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines. Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels. In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.

The Effect of Mobile Lifestyle Intervention Combined with High-Protein Meal Replacement on Liver Function in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Pilot Randomized Controlled Trial.

While many studies have explored dietary substitutes and mobile apps separately, a combined approach to metabolic dysfunction-associated steatotic liver disease (MASLD) has not been investigated. This study evaluated short-term mobile interventions coupled with partial meal replacement in patients with MASLD. Sixty adults with MASLD and a body mass index ≥25 kg/m2 from a health examination center were randomized into an intervention group using a mobile app with partial meal replacements or a control group receiving standard educational materials. Liver enzyme levels, lipid profiles, and anthropometric measurements were assessed at baseline and after 4 weeks. Twenty-five participants in the intervention group and 24 in the control group completed the trial. Significant reductions were observed in the intervention group for alanine aminotransferase (-28.32 versus [vs.] -10.67, p = 0.006) and gamma-glutamyl transferase (-27.76 vs. 2.79, p = 0.014). No significant changes in aspartate aminotransferase, body weight, or waist circumference were noted in the intervention group. Four weeks of mobile lifestyle intervention incorporating partial meal replacements improved liver enzyme profiles in patients with MASLD. This strategy demonstrated the potential for mitigating elevated liver enzyme levels without altering body weight or waist circumference. Comprehensive and longer-term research is needed to substantiate and elaborate these preliminary outcomes.

The Association of Serum Ferritin with Disease Severity in Non-alcoholic Fatty Liver Disease

Abstract Background NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. Aim of the Work The aim of this study is to evaluate the association of serum ferritin with non- alcoholic fatty liver disease. Patients and Methods The study was cross sectional study which conducted at Ain Shams University Hospital. This study was conducted on 80 patients both sexes, with age (18years old - 60 years), duration of study will be 6 months. All study patients approved to participate in this study. Patients were divided in to 2 groups as following: Results Our study reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD). Also ROC curve shows that the best cutoff point of serum ferritin to differentiate between normal lipid profile group and elevated lipid profile group was found > 80 with sensitivity of 82.5%, specificity of 60.0% and AUC of 69.5% while the best cutoff point of fatty liver index to differentiate between normal lipid profile group and elevated lipid profile group was found > 89 with sensitivity of 67.5%, specificity of 80.0% and AUC of 76.8%. Conclusion Elevated serum ferritin may reflect increased disease severity in NAFLD either because of increased ongoing hepatic or systemic inflammation or increased body iron stores or a combination of these factors. Our study also reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD).

Safety and Efficacy of Paxlovid in Pediatric Intensive Care Unit Patients with COVID-19.

Paxlovid (nirmatrelvir/ritonavir) has received endorsement from several guidelines for treating COVID-19 in adults, but its use in children is still uncertain. This study aimed to evaluate the safety and effectiveness of paxlovid in pediatric patients in the pediatric intensive care unit (PICU). A retrospective analysis was performed on children with COVID-19. The children who received paxlovid comprised the paxlovid group; otherwise, they were referred to as the control group. A total of 31 children were enrolled, with 12 and 19 participants assigned to the paxlovid and control groups, respectively. Approximately 35% had received vaccination against the novel coronavirus. The control group exhibited a significantly lower mean age in comparison to the paxlovid group (p < 0.001). However, no significant differences were observed between the groups in terms of other baseline data and biochemical indexes at admission. However, on the fifth day of drug administration, the paxlovid group exhibited a statistically significant decrease in temperature compared to the control group (p < 0.05). Additionally, the paxlovid group exhibited a significantly shorter conversion time to negativity for novel coronary genes in the respiratory tract (9.5 days) compared to the control group (16 days, p < 0.05). The administration of paxlovid did not result in any observed adverse reactions. Merely two patients exhibited a transient elevation in liver enzyme levels. The application of paxlovid in critically ill pediatric patients with COVID-19 can effectively control symptoms and promote virus clearance, demonstrating efficacy and a relatively low-risk profile.

Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

Objective: To explore the effect of black radish (Raphanus sativus L. var niger) root extract on liver enzymes, oxidative stress, and histopathological alterations in mice with sodium valproate-induced hepatotoxicity. Methods: Thirty-two mice were divided into four groups: the control group received drinking water by gavage, the second group was administered with 100 mg/kg of sodium valproate, the third group received 300 mg/kg of black radish root extract, and the fourth group was given both sodium valproate (100 mg/kg) and black radish root extract (300 mg/kg). After 28 days, the mice were euthanized, and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), along with liver malondialdehyde (MDA), reactive oxygen species (ROS), mitochondrial parameters, tumor necrosis factor-alpha (TNF-α) gene expression, and histopathological changes were assessed. Results: Sodium valproate caused hepatic damage in mice, characterized by elevated serum levels of liver enzymes, increased MDA and ROS levels and TNF-α gene expression, as well as histopathological alterations. The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST, MDA, ROS, TNF-α gene expression, as well as mitochondrial impairment, but did not have a significant effect on sodium valproate-induced histopathological changes. Conclusions: The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury, possibly through mitigating oxidative stress, mitochondrial impairment, and inflammatory mediator expression.

Utility of Radiological Follow Up of Main-Duct Intraductal Papillary Mucinous Neoplasms and Mixed-Type Intraductal Papillary Mucinous Neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) have the potential to evolve into pancreatic adenocarcinoma (PDAC). While main-duct IPMNs (MD-IPMNs), involving the main pancreatic duct (MPD), are less common than side-branch IPMNs (SB-IPMNs) or mixed-type IPMNs (mixed-IPMNs), their malignant transformation potential is far greater. Controversy exists between different guidelines in terms of recommended management strategies. This study was aimed at assessing the utility of the radiological follow up of MD-IPMNs and mixed-type IPMNs, including prevalence of worrisome radiological findings as well as clinical and laboratory parameters, and their correlation with the development of progression or pancreatic adenocarcinoma. Eighty-four patients with MD-IPMNs or mixed-type IPMNs who underwent at least one magnetic resonance cholangiopancreatography (MRCP) were included. Clinical and laboratory data were obtained retrospectively. A cross-sectional analysis was carried out to establish clinical and laboratory parameters associated with development of PDAC. A retrospective cohort analysis was performed on 44 patients who had at least six months of follow up, trying to identify factors correlating with worrisome radiological features. Nine cases (10.7%) of PDAC were recorded in this cohort. The laboratory and imaging factors associated with cyst size progression greater than 5 mm during follow up were elevated alanine transaminase (ALT) levels, the maximal cyst size, and the MPD diameter. Cross-sectional analysis indicated that PDAC was associated with nausea (p = 0.01), as well as increased levels of aspartate aminotransferase (AST) (p = 0.05), gamma glutamyl transpeptidase (GGT) (p = 0.01), and alkaline phosphatase (ALP) (p = 0.01). Elevated levels of liver enzymes were associated with IPMN progression and, subsequently, the development of PDAC. ALT levels, maximal cyst size, and MPD diameter are associated with the progression of cyst size. These data may aid in risk-stratifying patients when determining the follow up approach for IPMNs.

TBHQ mitigates fatty liver ischemia–reperfusion injury by activating Nrf2 to attenuate hepatocyte mitochondrial damage and macrophage STING activation

BackgroundLiver ischemia–reperfusion (IR) injury is an inevitable pathophysiological process in various liver surgeries. Previous studies have found that IR injury is exacerbated in fatty liver due to significant hepatocellular damage and macrophage inflammatory activation, though the underlying mechanisms are not fully understood. In this study, we aim to explore the role and mechanism of Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling in regulating hepatocellular damage and macrophage immune response in fatty liver IR injury. MethodsThe study used high-fat diet-induced fatty liver mice to establish an IR model, alongside an in vitro co-culture system of primary hepatocytes and macrophages. This approach was used to examine mitochondrial dysfunction, oxidative stress, mitochondrial DNA (mtDNA) release, and activation of macrophage STING (Stimulator of interferon genes) signaling. We also conducted recovery verification using H-151 (a STING inhibitor) and tBHQ (an Nrf2 activator). ResultsCompared to the control group, mice on a high-fat diet demonstrated more severe liver IR injury, as evidenced by increased histological damage, elevated liver enzyme levels, and heightened inflammatory markers. The HFD group showed significant oxidative stress and mitochondrial dysfunction and damage post-IR, as indicated by elevated levels of ROS and lipid peroxidation markers, and decreased antioxidant enzyme activity. Elevated mtDNA release from hepatocytes post-IR activated macrophage STING signaling, worsening inflammation and liver damage. However, STING signaling inhibition with H-151 in vivo or employing STING knockout macrophages significantly reduced these injuries. In-depth mechanism studies have found that the transfer of Nrf2 protein into the nucleus of liver cells after IR in fatty liver is reduced. Pre-treatment with tBHQ ameliorated liver oxidative stress, mitochondrial damage and suppressed the macrophage STING signaling activation. ConclusionsOur study reveals a novel mechanism where the interaction between hepatocellular damage and macrophage inflammation intensifies liver IR injury in fatty liver. Enhancing Nrf2 activation to protect mitochondrial from oxidative stress damage and inhibiting macrophage STING signaling activation emerge as promising strategies for clinical intervention in fatty liver IR injury.

Mitigation of cisplatin-induced hepatotoxicity by Salvia officinalis: Attenuation of oxidative damage and inflammation in rats

Salvia officinalis L., commonly known as sage and belonging to the Lamiaceae family, is a medicinal herb indigenous to the Mediterranean region. It is celebrated for its diverse pharmacological properties and traditional uses in folk medicine, particularly in addressing hepatotoxicity. Cisplatin (Cis), a potent chemotherapeutic agent widely employed in cancer treatment, is recognized for its efficacy but often accompanied by adverse effects, including hepatotoxicity. The aim of this study was to assess whether an ethanolic S. officinalis extract (ESOE) could provide protection against Cis-induced hepatotoxicity in an experimental rat model. The ESOE was prepared using standard extraction techniques, and its chemical constituents were elucidated through UPLC-ESI-MS/MS analysis, revealing the presence of bioactive compounds such as alkaloids, phenolic compounds, and flavonoids, which are associated with various therapeutic effects, including hepatoprotection. Adult male albino rats were allocated into four groups: control, ESOE (250 mg/kg), Cis (7.5 mg/kg), and ESOE (250 mg/kg) + Cis (7.5 mg/kg). The treatment duration lasted 21 days, with Cis administration on the 22nd day. Twenty-four hours post-Cis administration, blood and liver samples were collected for analysis. Cis-induced hepatotoxicity was evidenced by alterations in hematological parameters, including erythrocyte, thrombocyte, leukocyte, and lymphocyte counts, alongside elevated serum levels of liver enzymes (ALT, LDH, AST, ALP, and GGT), indicative of liver damage. Furthermore, Cis exposure resulted in increased hepatic malondialdehyde (MDA) and Nitric oxide (NO) levels, oxidative stress markers, coupled with decreased levels of reduced glutathione (GSH), a non-enzymatic antioxidant, and histopathological changes in liver tissue, characterized by necrosis and inflammation. Additionally, Cis treatment led to elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OH-dG), TNF-α, and IL-6, indicating oxidative stress and inflammation. Remarkably, pretreatment with ESOE ameliorated these Cis-induced hepatotoxic effects, as evidenced by improved hematological parameters, reduced liver enzyme activities, alleviated oxidative stress, and ameliorated histopathological alterations. The observed hepatoprotective effects of ESOE against Cis-induced liver injury may be attributed to its antioxidant and anti-inflammatory properties, highlighting its potential as a natural therapeutic agent in mitigating chemotherapy-associated hepatotoxicity.

Intrahepatic plasma cells, but not atypical memory B cells, associate with clinical phases of chronic hepatitis B.

Studies have traditionally focused on the role of T cells in chronic hepatitis B (CHB), but recent evidence supports a role for B cells. The enrichment of so-called atypical memory (AtM) B cells, which show reduced signaling and impaired differentiation, is believed to be a characteristic feature of CHB, potentially contributing to the observed dysfunctional anti-HBsAg B-cell responses. Our study, involving 62 CHB patients across clinical phases, identified AtM B cells expressing IFNLR1 and interferon-stimulated genes. Contrary to previous reports, we found relatively low frequencies of AtM B cells in the liver, comparable to peripheral blood. However, liver plasma cell frequencies were significantly higher, particularly during phases with elevated viral loads and liver enzyme levels. Liver plasma cells exhibited signs of active proliferation, especially in the immune active phase. Our findings suggest a potential role for plasma cells, alongside potential implications and consequences of local proliferation, within the livers of CHB patients. While the significance of AtM B cells remains uncertain, further investigation is warranted to determine their responsiveness to interferons and their role in CHB.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. We enrolled 343 816 adults aged ≥30years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend<0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend<0.001). Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Influence of elevated liver enzyme level on 30-day mortality rates in patients undergoing nonemergency orthopedic surgery

BackgroundThe effect of elevated preoperative liver enzyme levels on postoperative outcomes is a topic of concern to clinicians. This study explored the association between elevated preoperative liver enzyme levels and surgical outcomes in patients undergoing orthopedic surgery.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program database, we obtained data on adult patients who received nonemergency orthopedic surgery under general anesthesia between 2011 and 2021.ResultsWe evaluated the data of 477,524 patients, of whom 6.1% (24 197 patients) had elevated preoperative serum glutamic oxaloacetic transaminase (SGOT) levels. An elevated SGOT level was significantly associated with 30-day postoperative mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.39 to 1.90). We determined that the mortality rate rose with SGOT levels. The results remained unchanged after propensity score matching.ConclusionElevated preoperative SGOT levels constitute an independent risk factor for 30-day postoperative mortality and are proportionately associated with the risk of 30-day postoperative mortality.