GGT Levels Research Articles

Improvement of endorgan function following tricuspid edge-to-edge repair

Abstract Background/Introduction Subjects with severe tricuspid regurgitation (TR) often suffer from impaired endorgan function. The potential to improve endorgan function is an important goal of treatment. Purpose To assess baseline endorgan function and changes in organ function following transcatheter edge-to-edge repair with the TriClip device in subjects with severe TR from the TRILUMINATE Pivotal randomized controlled trial. Methods Right heart catheterization was required prior to enrollment; medication history was collected. Changes in biomarkers, including MELD-XI, GGT, eGFR, BUN, and TR and KCCQ overall summary score were assessed at baseline and 12-month follow-up for all enrolled subjects. A 15% improvement in biomarker levels was considered clinically relevant. The odds of achieving a 15% improvement in biomarkers between baseline and 12-month follow-up was compared between the Device and Control groups (presented as OR [95% CI]). Results A total of 572 subjects were enrolled and randomized. At baseline, subjects had elevated levels of GGT (83.0±87.7 U/L) and MELD-XI score (10.3±5.2), low eGFR (56.7±21.0 mL/min/1.73m2), and elevated BUN (29.5±16.7 mg/dL). Nearly 90% of subjects were on loop diuretics, with approximately 50% taking these in combination with a thiazide or potassium-sparing diuretic. The average diuretic dosage was 71 mg (furosemide equivalent). Most subjects had normal left ventricle ejection fraction (only 5% with LVEF <40%). Subjects had well-managed blood pressure (systolic: 122±13 mmHg, diastolic: 69±10), slightly elevated central venous pressures (12±6 mmHg), systolic pulmonary artery pressures (40±10 mmHg) and pulmonary capillary wedge pressures (15±4 mmHg), and normal transpulmonary gradients (11±4 mmHg). The odds of achieving a 15% improvement in liver and renal function was higher in TriClip patients compared to control: MELD-XI score (1.79 [1.22, 2.63]), GGT (1.83 [1.21, 2.77]), and eGFR (1.81 [1.18, 2.77]) - Fig 1. The favorable changes in organ function observed were also reflected when stratifying subjects by residual TR severity: The odds of a 15% biomarker improvement favored subjects with moderate or less residual TR for MELD-XI score (2.05 [1.39, 3.00]), GGT (1.91 [1.26, 2.90]), and eGFR (1.83 [1.20, 2.80]) compared with subjects who had severe or worse residual TR. Lastly, improvement in these biomarkers also favored subjects with a 15-point or greater improvement in KCCQ compared with subjects with less than a 15-point KCCQ improvement. Conclusions Use of TriClip in subjects with severe tricuspid regurgitation was associated with improvement in kidney and liver function, and this improvement was associated with reduction in the severity of TR. These data provide the first objective evidence of the physiologic impact of TR reduction obtained in a randomized clinical trial.

Characteristics of the proinflammatory response of monocytes/macrophages in patients with metabolic syndrome, exemplified by the production of IL-6 and MCP-1

Metabolic syndrome (MS) is one of the most common socially significant diseases. Around 1.9 billion people suffer from this disease, which places an enormous burden on healthcare systems around the world. This is particularly true in connection with concomitant diseases. With the progression of MS, disorders in the function of the immune system occur in the body, including those associated with mitochondrial dysfunction, leading to the development of chronic inflammation. In particular, there is an increase in the number of circulating monocytes actively recruited to inflamed adipose tissue, where there is non-specific proinflammatory activation of innate immune cells, which adopt an M1-like phenotype and become less sensitive to anti-inflammatory stimuli. This ultimately leads to a decrease in the functional activity of monocytes/macrophages and their immunoplasticity. The subject of the study was the venous blood of patients and the CD14+ monocytes/macrophages obtained from it by immunomagnetic separation. In our work, we focused on the search for significant relationships between markers of chronic inflammation and the formation of immune tolerance of monocytes/macrophages in patients with metabolic syndrome. Biochemical parameters, basal and LPS-stimulated production of proinflammatory cytokines (IL-6 and MCP-1) were investigated by culture of monocytes/macrophages in patients with metabolic syndrome. The evaluation of biochemical parameters in blood samples from MS patients and healthy donors revealed that the levels of ALAT, AST, GGT, alkaline phosphatase, uric acid, C-reactive protein, glucose and insulin were significantly higher in MS patients than in healthy donors. The levels of P-amylase and high-density lipoprotein were significantly lower than in the control group. Within the experimental model, repeated stimulation showed a decrease in cytokine production in response to LPS compared to the first stimulation on day 7. It was also found that the response to the primary stimulus was higher in cells from patients with a body mass index (BMI) 40 kg/m2, which could indirectly indicate the presence of a phenotype associated with chronic inflammation and consequently with reduced plasticity of the monocyte/macrophage immune response.

Outcomes of acute kidney injury continuum in children.

Acute kidney injury (AKI) is associated with high morbidity and mortality. The continuum of kidney damage after an AKI episode is poorly explored in the paediatric population. We performed a retrospective cohort study on 2346 children with AKI from a tertiary care hospital in Romania over a 9-year period. The main objective was to evaluate the impact of AKI duration on mortality and the risk of new-onset chronic kidney disease (CKD). Out of 2346 AKI patients, transient AKI was present in 655 patients (27.9%), persistent AKI in 1009 children (43%) and acute kidney disease in 682 patients (29.1%). In contrast to transient AKI, children who developed acute kidney disease were younger, with a higher degree of anaemia, lower number of platelets, higher procalcitonin, higher LDH, higher GGT, higher urea and higher serum creatinine levels. The pre-renal cause of AKI was the leading cause regardless of AKI duration. As kidney injury progressed over time, there was an increasing incidence of the intrinsic causes of AKI (11.1% in transient AKI, 13.2% in persistent AKI and 22.6% in acute kidney disease). Acute kidney disease patients had the highest mortality rate (16.42%), followed by transient AKI (14.66%) and persistent AKI (9.81%). Overall mortality increased in the presence of renal microvascular alterations, acute tubular necrosis, lower haemoglobin, serum proteins and platelets, and higher procalcitonin levels. The continuum of AKI expressed as acute kidney disease resulted in an increased risk of new-onset CKD. CKD was influenced by the intrinsic cause of AKI and not by AKI severity.

Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies.

Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses. Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses. In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes. Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.

New model to predict survival in advanced pancreatic ductal adenocarcinoma patients by measuring GGT and LDH levels and monocyte count.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed. This retrospective study assesses the prognostic value of blood biomarkers in advanced and metastatic PDAC patients (n=96) from Spain. Cut-off points for hematological parameters were calculated and correlated with overall survival (OS) using Kaplan-Meier, log-rank test, robust Cox proportional hazards and logistic regressions. In univariate analysis, individuals with low levels of GGT, LDH, ALP, leukocyte-, neutrophil- and monocyte counts showed significantly longer survival than patients with higher levels. In multivariate analysis, lower levels of GGT (HR (95%CI), 2.734 (1.223-6.111); p=0.014), LDH (HR (95%CI), 1.876 (1.035-3.400); p=0.038) and monocyte count (HR (95%CI), 1.657 (1.095-2.506); p = 0.017) remained significantly beneficial. In consequence, we propose a prognostic model based on logistic regression (AUC=0.741) of these three biomarkers as a pioneer tool to estimate OS in PDAC. This study has demonstrated that the joint use of GGT (<92.00), LDH (<220.00) and monocyte count (<800) are independent positive prognostic factors in PDAC that can predict one-year survival in a novel prognostic logistic model.

Subacute Toxicity and Pharmacokinetic Evaluation of the Synthetic Cannabinoid 4F-MDMB-BUTINACA in Rats: A Forensic and Toxicological Perspective

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p &lt; 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart.

Choline-deficient, high-fat diet-induced MASH in Göttingen Minipigs: characterization and effects of a chow reversal period.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies. Furthermore, changes in hepatic gene expression during the experiment were explored by RNA sequencing. For a subset of the minipigs, the diet was changed from CDAHFD back to chow to investigate whether the liver pathology was reversible. Göttingen Minipigs on CDAHFD gained body weight, and plasma levels of cholesterol, AST, ALT, ALP, and GGT were increased. CDAHFD-fed minipigs developed hepatic steatosis, inflammation, and fibrosis, which in 5 of 16 animals progressed to cirrhosis. During an 11-wk chow reversal period, steatosis regressed, while fibrosis persisted. Regarding inflammation, the findings were less clear, depending on the type of readout. MASH Human Proximity Scoring (combined evaluation of transcriptional, phenotypic, and histopathological parameters) showed that CDAHFD-fed Göttingen Minipigs resemble human MASLD/MASH better than most rodent models. In conclusion, CDAHFD-fed minipigs develop a MASH-like phenotype, which, in several aspects, resembles the changes observed in human patients with MASLD/MASH. Furthermore, repeated collection of liver biopsies allows detailed characterization of histopathological changes over time in individual animals.NEW & NOTEWORTHY The physiology and metabolism of pigs have a relatively high resemblance to humans. This study characterizes a new animal model of MASLD/MASH using CDAHFD-fed Göttingen Minipigs. Göttingen Minipigs fed CDAHFD gained weight and developed hepatic steatosis, inflammation, fibrosis, and cirrhosis. After an 11-wk chow-reversal period, hepatic steatosis and some inflammatory parameters reversed. Combined evaluation of phenotypic, transcriptional, and histological parameters revealed the minipig model showed a higher resemblance to human disease than many rodent models.

Paediatric-onset autoimmune liver disease: Insights from a monocentric experience

BackgroundAutoimmune liver disease (AILD) encompasses autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC) and primary sclerosing cholangitis (PSC). A unified disease process evolving over time through these entities has been recently suggested. From this perspective, this study aimed to compare the characteristics of childhood-onset AILD at baseline and after a medium-to-long term follow-up period. MethodsPaediatric-onset cases of AILD diagnosed between 1992 and 2023 at a tertiary-care centre were reviewed. Patients transitioned to adult-care by the time of data collection were asked for clinical updates. ResultsFifty-five patients were included (AIH = 20, ASC =22, PSC =13). AIH, ASC and PSC exhibited increasing age at the onset (AIH to PSC, p < 0.01). The area under the receiver operating characteristic curve for gamma-glutamyltranspeptidase (GGT) combined with alkaline phosphatase/aspartate aminotransferase (ALP/AST) ratio in predicting sclerosing cholangitis was 0.94, with a sensitivity of 86 % and a specificity of 94 %. At the last follow-up (median duration 5,8 years, interquartile range [IQR] 2,9–10,2, n = 45), 15 patients (33 %) developed portal hypertension, 2 patients (4 %) underwent liver transplantation, no patient died. ConclusionA cohort of childhood-onset AILD managed at a single centre reveals a temporal trend in the onset of AIH, ASC and PSC, with progressively older ages. Elevated GGT levels combined with a high ALP/AST ratio predict the diagnosis of sclerosing cholangitis. The occurrence of liver-related adverse events in one-third of patients highlights the progressive nature of paediatric-onset AILD.

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study.

Changes in alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) levels in patients with primary liver cancer (PLC) after radiofrequency ablation (RFA). Hepatocellular carcinoma is a malignant tumor with high incidence worldwide. As a common local treatment, RFA has attracted much attention for its efficacy and influence on liver function. To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA. The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected. The chi-square test was used to compare the data between groups. The Kaplan-Meier method and Cox regression were used to analyze the associations between serum ALP and GGT levels and overall survival, progression-free survival (PFS) and clinical characteristics of patients before treatment. The 1-year survival rates of patients with normal (≤ 135 U/L) and abnormal (> 135 U/L) serum ALP before treatment were 91% and 79%, respectively; the 2-year survival rates were 90% and 68%, respectively; and the 5-year survival rates were 35% and 18%, respectively. The difference between the two groups was statistically significant (P = 0.01). Before treatment, the 1-year survival rates of patients with normal serum GGT levels (≤ 45 U/L) and abnormal serum GGT levels (> 45 U/L) were 95% and 87%, the 2-year survival rates were 85% and 71%, and the 5-year survival rates were 37% and 21%, respectively. The difference between the two groups was statistically significant (P < 0.001). Serum ALP [hazard ratio (HR) = 1.766, 95% confidence interval (95%CI): 1.068-2.921, P = 0.027] and GGT (HR = 2. 312, 95%CI: 1.367-3.912, P = 0.002) is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor. The 1-year PFS rates were 72% and 50%, the 2-year PFS rates were 52% and 21%, and the 5-year PFS rates were 14% and 3%, respectively. The difference between the two groups was statistically significant (P < 0001). The 1-year PFS rates were 81% and 56% in patients with normal and abnormal serum GGT levels before treatment, respectively; the 2-year PFS rates were 62% and 35%, respectively; and the 5-year PFS rates were 18% and 7%, respectively, with statistical significance between the two groups (P < 0.001). The serum ALP concentration (HR = 1. 653, 95%CI: 1.001-2.729, P = 0.049) and GGT (HR = 1.949, 95%CI: 1.296-2.930, P = 0.001) was closely associated with PFS after RFA in patients with PLC. The proportion of male patients with abnormal ALP levels is high, the Child-Pugh grade of liver function is poor, and the incidence of ascites is high. Among GGT-abnormal patients, the Child-Pugh grade of liver function was poor, the tumor stage was late, the proportion of patients with tumors ≥ 5 cm was high, and the incidence of hepatic encephalopathy was high. Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA, and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

Measles-Clinical and Biological Manifestations in Adult Patients, Including a Focus on the Hepatic Involvement: Results from a Single-Center Observational Cohort Study from Romania.

Background: Hepatic involvement in measles, particularly among adolescents and adults, has been recognized since 1960. This involvement typically manifests during the eruptive phase of the disease and is primarily characterized by hepatocellular dysfunction, with jaundice being a less common occurrence. Studies have reported hepatic involvement in 80-86% of measles cases among young adults associated with severe forms of the disease with intra-infectious hepatitis. Recent data from Romania indicated 20,035 confirmed measles cases between January and June 2024, including 17 fatalities and significant hepatic alterations. These findings underscore the need for the further investigation of the hepatic manifestations of measles. The primary objective of our study was to evaluate the clinical and baseline characteristics of the enrolled patients with a brief assessment of liver impairment. Methods: In light of these observations, we conducted a retrospective analysis between 1 November 2023 and 15 June 2024 in patients aged >16 years who were confirmed, by the detection of measles IgM in serum samples, to have acute measles infection and hospitalization. Results: During the study period, 71 hospitalized patients were diagnosed with measles, of whom 37 were female (52.1%), with ages ranging from 16 to 64 years (mean age 34.21 years). Most cases (77.5%) exhibited moderate clinical forms of measles, while 22.5% had severe forms. Respiratory failure requiring oxygen therapy was uncommon (25.4% of severe pneumonia cases). Although a Pearson chi-square test indicated no significant association between the presence of pneumonia and clinical form (p = 0.066), the likelihood ratio test suggested a potential link (p = 0.018). Hepatic involvement was common with elevated AST (87.3%) and ALT (76%) levels. Jaundice was observed in 12.7% of patients. GGT changes were noted in 35.2% of cases, with significant correlations between GGT levels and disease severity (p = 0.001). Analysis of various symptoms revealed significant associations between nausea, dyspnea, and severe clinical forms. Anorexia, diarrhea, and nausea were the most frequently reported symptoms. Thrombocytopenia was observed in 11 patients, with no significant correlation with disease severity. Comorbidities, such as COPD, were significantly associated with disease severity (p = 0.010). Conclusions: Our findings highlight that, while cytolytic hepatic damage is a typical response to measles infection, cholestatic involvement may serve as an indicator of more severe disease progression.

Prognostic model for predicting recurrence in hepatocellular carcinoma patients with high systemic immune-inflammation index based on machine learning in a multicenter study.

This study aims to use machine learning to conduct in-depth analysis of key factors affecting the recurrence of HCC patients with high preoperative systemic immune-inflammation index (SII) levels after receiving ablation treatment, and based on this, construct a nomogram model for predicting recurrence-free survival (RFS) of patients. This study included clinical data of 505 HCC patients who underwent ablation therapy at Beijing You'an Hospital from January 2014 to January 2020, and accepted 65 HCC patients with high SII levels from Beijing Ditan Hospital as an external validation cohort. 505 patients from Beijing You'an Hospital were divided into low SII and high SII groups based on the optimal cutoff value of SII scores. The high SII group was further randomly divided into training and validation cohorts in a 7:3 ratio. eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox regression analysis, were used to explore the factors affecting the post-ablation RFS of HCC patients. Based on the identified key factors, a nomogram model were developed to predict RFS in HCC patients, and their performance were evaluated using the concordance index (C index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). The optimal cutoff value for nomogram scores was used to divide patients into low- and high-risk groups, and the effectiveness of the model in risk stratification was evaluated using Kaplan-Meier (KM) survival curves. This study confirmed that age, BCLC stage, tumor number, and GGT level were independent risk factors affecting RFS in HCC patients. Based on the selected risk factors, an RFS nomogram was successfully constructed. The C-index, ROC curve, calibration curve, and DCA curve each demonstrated the discrimination, accuracy, and decision-making utility of the nomogram, indicating that it has good predictive performance. KM curve revealed the nomogram could significantly differentiate patient populations with different recurrence risk. We developed a reliable nomogram that can accurately predict the 1-, 3-, and 5-year RFS for HCC patients with high SII levels following ablation therapy.

Apocynin alleviates thioacetamide-induced acute liver injury: Role of NOX1/NOX4/NF-κB/NLRP3 pathways

The liver has a distinctive capacity to regenerate, yet severe acute injury can be life-threatening if not treated appropriately. Inflammation and oxidative stress are central processes implicated in the pathophysiology of acute livery injury. NOX isoforms are important enzymes for ROS generation, NF-κB and NLRP3 activation, its inhibition could be vital in alleviating acute liver injury (ALI). Here in our study, we used apocynin, a natural occurring potent NOX inhibitor, to exploreits potential protective effect against thioacetamide (TAA)-induced ALI through modulating crucial oxidative and inflammatory pathways. Rats were injected once with TAA (500 mg/kg/i.p) and treated with apocynin (10 mg/kg/i.p) twice before TAA challenge. Sera and hepatic tissues were collected for biochemical, mRNA expression, western blot analysis and histopathological assessments. Pretreatment with apocynin improved liver dysfunction evidenced by decreased levels of aminotransferases, ALP, GGT and bilirubin. Apocynin reduced mRNA expression of NOX1 and NOX4 which in turn alleviated oxidative stress, as shown by reduction in MDA and NOx levels, and elevation in GSH levels andcatalase and SOD activities. Moreover, apocynin significantly reduced MPO gene expression. We also demonstrate that apocynin ameliorated inflammation through activating IκBα and suppressing IKKα, IKKβ, NF-κBp65 and p-NF-κBp65, IL-6 andTNF-α. Additionally, apocynin potentiated the gene expression of anti-inflammatory IL-10 and reduced levels of hepatic NLRP3, Caspase-1 and IL-1β. These results suggest that apocynin protects against ALI in association with the inhibition of NOX1 and NOX4 and regulating oxidative and inflammatory pathways.

Boosting impacts of Acacia nilotica against hepatic toxicity induced by gentamicin: biochemical, anti-inflammatory and immunohistochemical study.

It seems that gentamicin's toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN's extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.

Congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variation in 2 cases and literature review

Objective: To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation. Methods: This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children's Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized. Results: Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy. Conclusions: BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.

Should Serum Levels of Creatine Kinase be Evaluated in Patients with Acne Vulgaris Treated with Systemic Isotretinoin

The laboratory tests that should be performed and their frequency during isotretinoin treatment are controversial. We wanted to investigate muscle and joint pain and laboratory tests in acne patients who received isotretinoin. Between April 2019 and February 2023, serum CK, AST, ALT, and GGT levels were retrospectively evaluated in acne patients before and three months after systemic isotretinoin treatment. This study included 410 patients. The median serum AST, ALT, and GGT levels significantly increased, whereas serum CK levels were similar in all patients three months after treatment. 23 (5.6%) patients revealed muscle or joint pain after treatment. No significant difference was detected in patients with or without pain in the median serum CK, AST, ALT, and GGT levels after treatment. Isotretinoin treatment at a dose of 10 mg/day was more common in patients with pain than in those without pain, whereas none of the patients who received isotretinoin 40 mg/day developed muscle or joint pain. We suggest that routine evaluation of serum CK levels is unnecessary in acne patients treated with isotretinoin. However, muscle and joint pain may develop even at doses as low as 10 mg/day. Furthermore, monitoring AST, ALT, and GGT levels may be beneficial in acne patients treated with isotretinoin.

The Predictive Value of Gamma-Glutamyl Transferase on Jaundice Clearance in Biliary Atresia: An Evidence-Based Case Report and Meta-Analysis

Background: Biliary atresia (BA) is a neonatal condition characterized by the obstruction of extrahepatic bile ducts. Case: A 2-year-old female with BA underwent a Kasai procedure at 3 months of age. Despite the surgery, she developed persistent jaundice and abdominal enlargement. Preoperative laboratory findings revealed elevated liver enzymes, GGT, and bilirubin levels. This case raises the clinical question of whether preoperative GGT levels can predict JC after the Kasai procedure, in addition to its role in diagnosis. Methods: A systematic literature search was performed on 4 databases (PubMed, Scopus, Cochrane, and Proquest) by using relevant keywords and identified seven high quality studies. Results: Five studies found higher GGT levels in patients who achieved JC following Kasai surgery, compared to those with unsuccessful jaundice clearance (JUC). However, two studies reported conflicting findings. A pooled analysis indicated a non-significant trend toward higher GGT levels in the JC group compared to the JUC group (WMD: 65.6, 95% CI: -58.6; 189.8). Conclusion: Elevated preoperative GGT levels may be associated with improved JC in BA patients. However, further investigation to validate these findings, determine the optimal role of GGT in assessing prognosis, and later, guiding treatment decisions in BA patients.

Metabolic Risk in Patients with a Diminished Ovarian Reserve and Premature Ovarian Insufficiency.

Objective: Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) represent conditions of different severity, characterized by an earlier-than-expected decrease in ovarian activity. The present study aims to compare metabolic disturbances between women with DOR and patients with POI from a different origin. Materials and methods: A total of 226 women (28 healthy women; 77 individuals with DOR, and 121 patients with POI/36 with Turner syndrome [TS] and 85 with non-TS POI/) have been studied retrospectively. Data concerning anthropometric indices, and metabolic parameters were collected. Results: Patients with DOR, non-TS POI, and TS had increased blood pressure and liver enzymes, pronounced insulin resistance, and worse lipid profiles than controls (p < 0.008 for all). TS patients had significantly higher ASAT, GGT, and TSH levels compared to non-TS POI and DOR individuals. The prevalence of type 2 diabetes tended to be higher in TS women compared to other groups. The prevalence of previously diagnosed polycystic ovarian syndrome was lower in the non-TS POI patients than in the DOR patients (p = 0.005). Conclusions: patients with decreased ovarian function suffer from insulin resistance, abnormal lipid profile, and subtle hepatic disturbances, irrespective of the severity of the condition and the presence of chromosomal aberrations.

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

The Feasibility of using Liver Function Indices and FibroScan in combination to predict the occurrence of anti-tuberculosis drug-induced liver injury in patients with liver disease

Background: The study aims to assess the feasibility of using a combined approach of liver function indices and FibroScan measurements as a predictive tool for the early detection of anti-tuberculosis drug-induced liver injury (DILI) in patients with existing liver disease. Methods: A retrospective cohort study was conducted, including adult tuberculosis patients with documented liver disease. Liver function was assessed using standard biochemical parameters, and FibroScan examinations were performed to determine liver stiffness measurement (LSM). Patients were monitored for clinical and biochemical signs of DILI throughout treatment. Logistic regression models and Receiver Operating Characteristic (ROC) curves were used for data analysis. Statistical significance was set at p &lt; 0.05. Results: Patients who developed DILI showed significantly higher levels of ALT, AST, total bilirubin, GGT, and LSM, with strong positive correlations between these markers and DILI occurrence. Logistic regression analysis revealed elevated ALT, AST, TBIL, and GGT were strongly associated with an increased likelihood of DILI. The area under the ROC curves indicated excellent predictive accuracy of these parameters. A nomogram for predicting DILI based on the combined biomarkers was established. Conclusion: The study demonstrates the feasibility of utilizing liver function indices and FibroScan measurements in combination to predict anti-tuberculosis DILI. The results highlight the importance of baseline liver health assessment and offer promising implications for clinical practice, aiding in individualized risk estimation and therapeutic decision-making for patients with liver disease initiating anti-tuberculosis therapy. Further validation in larger cohorts is warranted to strengthen the predictive model.

Efficacy and Safety of BoozLiv™ as an add on therapy in patients with alcoholic liver disease: An open-label, randomized controlled trial

BackgroundAlcoholic Liver Disease (ALD) poses a significant global health threat, contributing to millions of deaths each year. Despite the well-established link between chronic alcohol consumption and liver damage, treatment options remain limited, emphasizing the need for innovative approaches. MethodsAn open-label, randomized controlled trial was conducted in India, involving 68 adult ALD patients over a 12-week period. The patients were randomized into two groups: one receiving standard therapy and the other receiving standard therapy along with BoozLiv™ syrup. Liver function tests, Model for End-Stage Liver Disease (MELD) scores, and safety parameters were assessed at various intervals. ResultsThe study demonstrated that BoozLiv™ syrup, as an add-on therapy, significantly reduced total bilirubin, direct bilirubin, SGOT, SGPT, ALP, and GGT levels compared to standard therapy alone (p ​< ​0.05). The MELD score, indicative of liver function, showed a substantial improvement in the BoozLiv™ group (p ​< ​0.01). Safety analysis revealed that BoozLiv™ was well-tolerated, with only minor adverse effects such as nausea and vomiting reported. ConclusionBoozLiv™ syrup, used in conjunction with standard therapy, showed promising results in improving liver function and reducing liver damage markers in ALD patients. The safety profile was favorable and no patient has withdrawn their consent due to adverse events. Further long-term studies in larger populations are warranted to validate these findings and establish BoozLiv™ as a potential therapeutic option for ALD.