Elevated Gamma-glutamyl Transferase Research Articles

Interpreting elevated liver blood test results through a genetic lens: A genome-wide association study.

Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs). A genome-wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an 'elevated' LBT-and how this differs by PGS-was assessed through competing risk survival analysis. This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10-year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma-glutamyltransferase (GGT) and the 10-year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10-year risk was .38%. Accordingly, the 10-year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis-4 index, total bilirubin, and platelet count. Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.

Gamma-glutamyl transferase to aspartate aminotransferase ratio (GSR) predicts prognoses in patients with colorectal cancer with liver metastasis after microwave ablation

BackgroundMicrowave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA.MethodsA retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses.ResultsHigh GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS.ConclusionsOur findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA.Trial registrationNot applicable.

Assessment of abnormal liver function tests and associated factors among COVID-19-infected patients in Addis Ababa, Ethiopia, 2022: a facility-based comparative cross-sectional study

ObjectiveLiver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities...

Evaluation of maternal bromoform supplementation in late gestation on blood parameters of cows and their progeny

Bromoform supplementation has been successful in reducing enteric methanogenesis in ruminants; however, the impacts on the health of these animals are still limited. The current study evaluates the impact of maternal bromoform supplementation on the health of late-gestation cows and their progeny. Pregnant Angus cows (n = 42) were allocated into a control or bromoform group (n = 21 cows per treatment). Bromoform extracted from Asparagopsis armata (7,372 mg/kg) was supplemented once daily. Blood samples were collected from cows before supplementation (baseline). Within 24 h of parturition, blood and colostrum samples were collected from each cow and blood from neonates. Colostrum brix was measured to indicate immunoglobulin content. All data was analysed using the MIXED procedure in SAS.Supplementation of cows with bromoform resulted in increased blood urea to creatinine ratio (P = 0.048), base excess (P = 0.049), total carbon dioxide (TCO2; P = 0.048) and a decrease in blood glutamate dehydrogenase (GLDH; P = 0.031) compared to the control group. For cows in the bromoform group, a trend was observed for higher levels of partial pressure of carbon dioxide (pCO2; P = 0.070) and bicarbonate (HCO3-; P = 0.052), and lower levels of partial pressure of oxygen (pO2; P = 0.058) compared to the control group. Blood gamma-glutamyl transferase (GGT) was elevated in offspring of cows fed bromoform (P = 0.050). The lower blood pO2 of pregnant cows fed bromoform and elevated blood GGT levels in offspring are not well understood and highlight the need for further investigation. Additionally, the low-dose bromoform supplementation affected various blood gas parameters of cows and calves, demonstrating the importance of monitoring these parameters when using different doses of halogenated compounds in livestock.

Study of serum gamma glutamyl transferase in acute stroke - a single centre experience

Background: Gamma-glutamyl transferase (GGT) is an enzyme involved in oxidative stress and inflammation, which are key mechanisms in the pathogenesis of stroke. Recent evidence suggests serum GGT levels may be associated with the risk and prognosis of acute ischemic stroke. This study aimed to investigate serum GGT levels in patients with acute stroke at a single center in India. Methods: This case-control study included 100 patients (50 with acute stroke and 50 age and sex-matched controls). Patients aged 40 to 80 years and diagnosed with acute stroke (encompassing first-time occurrences of intracerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage) were included in the study. Serum GGT levels were compared between stroke patients and controls. The association of GGT with various risk factors was also analyzed among cases. Results: The mean age of cases is 60.2±10.07 years. Hemorrhagic stroke was most common and found in 52% of cases. Mean serum GGT levels were significantly higher in stroke patients (55.2540±40.8909 U/l). Higher serum GGT levels were associated with male gender, presence of diabetes, hypertension, dyslipidemia and smoking and were found to be statistically significant (p&lt;0.005). Age and stroke type were found to be not significantly associated with GGT levels. Conclusions: In conclusion, our study findings indicate that elevated serum GGT levels are associated with an increased risk of stroke, particularly in male patients and those with hypertension, dyslipidemia, and diabetes. Further prospective studies are needed to establish the predictive value of GGT for stroke.

Automated Fibrosis-4 Index: Simplifying Non-Alcoholic Fatty Liver Disease for Diabetologists.

Background and Objectives: Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (55%) and are at increased risk for developing non-alcoholic steatohepatitis, a severe form of NAFLD. Early detection of advanced fibrosis in patients with T2D and NAFLD is crucial and can prevent progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. However, screening for liver disease and risk-stratification pathways are not established in patients with T2D. We evaluated the efficacy of using the automated fibrosis-4 (FIB-4) index in routine clinical settings to identify patients requiring further specialist evaluation. Materials and Methods: In this prospective cohort study, individuals diagnosed with T2D were recruited from diabetes clinics at a tertiary university hospital. Demographic, clinical, and laboratory data were comprehensively collected. The FIB-4 index was automatically calculated and integrated into the hospital's electronic medical records (EMRs), which were then stratified by age. Patients with advanced fibrosis (FIB-4 index ≥ 1.3) were referred to a specialist. Student's t-test or the Mann-Whitney U test was used to analyze variables associated with advanced fibrosis. Logistic regression was used to identify predictors of advanced fibrosis. Results: Among the 318 patients with T2D, 9.7% had advanced fibrosis. The majority were females (54.7%) and Saudi nationals (89.6%). Several factors, including age, platelet count, total bilirubin, serum albumin, total cholesterol, low-density lipoprotein, transaminases, and gamma-glutamyl transferase (GGT), showed significant associations with advanced fibrosis (all p < 0.05). Older age, elevated total bilirubin and GGT levels, and prolonged international normalized ratio emerged as independent predictors of advanced fibrosis. Conclusions: Integrating the FIB-4 index into the EMR during the routine care of patients with T2D proved to be a valuable tool in effectively identifying individuals at risk of advanced fibrosis. Our findings emphasize the need for further research to refine screening strategies in this high-risk population.

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

BACKGROUND AND AIMPorto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension (PH). Liver biopsy (LB) is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyl transferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. METHODSThe study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021. RESULTS144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only twelve (8.3%) had liver stiffness measurements (LSM) >10 kPa, 7 (4.8%) had ultrasound PH evidence. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%). Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio, OR = 2.60, 95% confidence interval, CI: 1.13-5.99), LSM < 10 kPa (OR = 11.05, 95% CI: 2.16-56.66) and GGT < 200 U/L (OR = 2.69, 95% CI: 1.22-5.98). CONCLUSIONSPSVD was the main cause of persistent and unexplained elevation of GGT. Male sex, LSM < 10kPa and GGT < 200U/l were associated with PSVD. These findings highlight the role of LB in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation. IMPACT AND IMPLICATIONSIn outpatient settings, it is common to encounter subjects with persistent and unexplained GGT elevation. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder (PSVD) among these subjects when they undergo liver biopsy. Male sex, liver stiffness measurement (LSM) < 10 kPa, and GGT < 200 IU/L predict this histological finding.These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension (PH). Additionally, the data may encourage further studies in the field of PSVD, particularly to define its clinical evolution in patients without signs of PH at diagnosis.

Phase I clinical study of FC084CSA, a high selective AXL kinase inhibitor that ameliorates tumor microenvironment and augments the effectivity of immunotherapy.

e15116 Background: NSCLC patients with STK11 gene mutations could not benefit from immunotherapy, according to the data of multiple clinical trials. This is associated with immunosuppressive tumor microenvironment (TME) due to elevated AXL expression, and deficiency in pro-inflammatory cytokines and effector T cells. AXL inhibitor bemcentinib (formerly BGB324) has been found to improve the effectiveness of immunotherapy of immune checkpoint inhibitors. FC084CSA is a high selective AXL inhibitor. Methods: This is an ongoing first-in-human, phase I study of FC084CSA in patients with advanced solid tumors. The primary objective is to evaluate the safety and tolerability of FC084CSA. The secondary objectives include preliminary efficacy and pharmacokinetics. Results: As of January 10th, 2024, 9 patients with a median age of 60 years (44-73) were enrolled in 4 different dose levels: 100mg QD, 200mg QD, 400mg QD and 600mg QD. All patients had ≥ 2 prior lines of prior therapy. No dosing-limiting toxicities were observed. 8 (88.9%) patients experienced treatment-related adverse events (TRAEs). Most TRAEs were grade 1 or 2 and only one grade 3 TRAE was observed. The most common TRAEs (≥20%) included increased blood lactate dehydrogenase (44.4%), elevated gamma-glutamyl transferase (33.3%), proteinuria (33.3%), anemia (33.3%), increased aspartate aminotransferase (22.2%), weight loss (22.2%), increased blood creatinine (22.2%) and vomiting (22.2%). A total of 8 patients had at least 1 post-baseline tumor assessment. Objective response rate (ORR) was 0% and disease control rate (DCR) was 62.5% (5/8). Conclusions: FC084CSA was well tolerated in patients with previously heavily treated solid tumors. Clinical trial information: NCT06231550 .

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

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

Maralixibat (Livmarli)

CADTH recommends that Livmarli should be reimbursed by public drug plans for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) if certain conditions are met. Livmarli should only be covered to treat patients aged 12 months and older with a diagnosis of ALGS and who have impaired bile flow demonstrated by at least 1 of the following: elevated serum bile acids (sBAs), conjugated bilirubin, or gamma-glutamyl transferase; fat-soluble vitamin deficiency; and/or intractable itch. Patients must experience moderate to severe itch symptoms and must be currently or have been previously treated with systemic medication for itch. Livmarli should only be reimbursed if it is prescribed under the care of a specialist with experience in managing ALGS, if patients experience an improvement in their itching after using Livmarli for 6 months, and if the cost of Livmarli is reduced. Livmarli should be stopped if the patient receives a liver transplant or biliary diversion surgery.

Psoriasis Area and Severity Index and its Correlation with Liver Function Test

Objective: To determine Psoriasis Area and Severity Index score and its association with LFT values in patients of psoriasis. Methodology: This cross-sectional study, was done on patients visiting the skin OPD of LUMHS Jamshoro/Hyderabad. Diagnosed patients of Psoriasis, aged between 18 and 50 years and both genders were included. A 5cc blood sample was collected from each individual to evaluate the LFT. Psoriasis Area and Severity Index (PASI) scores was defined based on the percentage of body surface area affected by psoriasis lesion. All the information was entered and analyzed using SPSS version 26. Results: The mean age of the patients was 44.81±11.10 years. Out of the total 102 patients, 74.5% were male patients and 25.5% were female. The mean duration of psoriasis was 6.46 ± 4.49 years. Out of all 32.4% had mild psoriasis (PASI &lt; 7), 40.2% had moderate psoriasis (PASI 8-12), and 27.5% had severe psoriasis (PASI &gt; 12). Regarding LFT values, 73.5% had elevated alanine transaminase (ALT), 32.4% had elevated aspartate transaminase (AST), 70.6% had elevated alkaline phosphatase (ALP), 68.6% had elevated bilirubin, and 67.6% had elevated gamma-glutamyl transferase (GGT). AST and GGT levels rise significantly linked to PASI (p- &lt;0.05). Conversely, for ALP and Bilirubin levels, there is no significant difference across severity of PASI (p- &gt;0.05). Conclusion: Patients with severe psoriasis exhibit a predisposition to hepatic dysfunction. Study observed abnormalities in liver function tests (LFT) among psoriatic patients, suggesting a potential link to liver disease development.

Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines

Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations.

Gamma-Glutamyl Transferase and the Risk of Type 2 Diabetes Mellitus: A Review

The relationship between gamma-glutamyl transferase (GGT) levels and risk factors for type 2 diabetes mellitus (T2DM) and the risk of incident T2DM was assessed using a narrative review of available evidence. Higher circulating levels of GGT are associated with an increased risk of type 2 diabetes mellitus, suggesting GGT as a risk predictor of T2DM. The incidence of type 2 diabetes and its association with GGT elevation could be explained by oxidative stress in cells followed by subclinical inflammation and fatty liver, leading to impaired insulin secretion and insulin resistance. A strong correlation is evident between BMI and GGT, in which hepatic steatosis and insulin resistance are proposed to be the intermediate connecting characteristics.

Independent and additive effects of binge drinking and obesity on liver enzymes: a cross-sectional analysis using the Korean National Health Insurance Service data.

Binge drinking (BD) has been associated with elevated liver enzymes, but the joint association of BD and adiposity with liver enzymes is understudied. We aimed to examine the combined association of BD and obesity with elevated liver enzymes. Data were obtained from 285,600 patients in the Korean National Health check-up program during 2009-2015. Level I BD (BDI) was defined as alcohol consumption of >60 g (men) or >40 g (women) on one occasion in the previous year. High-intensity BD (HIBD) corresponded to at least two times the BDI levels. General and abdominal obesity were defined by body mass index and waist circumference. Logistic regression was used to examine the independent and joint associations of BD and obesity with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Relative excess risk (RERI), attributable proportion (AP), and synergy index (SI) were calculated to estimate the additive interaction effects. The mean age was 42.1 ± 0.03 years and 50.2% were women. Elevated ALT [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.16], AST (OR 1.16, 95% CI 1.11-1.23), and GGT (OR 1.84, 95% CI 1.05-1.94) were associated with HIBD. Higher odds of elevated ALT (OR 3.57, 95% CI 3.43-3.71), AST (OR 3.47, 95% CI 3.37-3.58), and GGT (OR 2.10, 95% CI 1.98-2.12) were observed in individuals with general obesity. A similar trend was observed for abdominal obesity. The RERI, AP, and SI for the interaction effect of BD and general obesity were 23%, 7%, and 13% for elevated AST levels, and 67%, 24%, and 58% for elevated GGT levels, respectively. Similar effects were observed for the interaction between BD and abdominal obesity. Obesity aggravated the odds of elevated liver AST and GGT levels in HIBD.

Gamma-glutamyl transferase and calculus of kidney incidence: a Mendelian randomization study

Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016–1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070–1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002–1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020–1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.

Association between polycyclic aromatic hydrocarbon exposure and liver function: The mediating roles of inflammation and oxidative stress

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects.

Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study.

Researchers have suggested a potential relationship between gamma-glutamyl transferase (GGT) level and stroke. We investigated a potential causal relationship between GGT level as exposures and stroke and stroke subtypes (cardioembolic, small vessel, and large artery) in a European population. We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) data from the UK Biobank as the exposure set. For the outcome set, we used stroke in the GWAS data from the GIGASTROKE Consortium. We considered alcohol consumption, atrial fibrillation, and body mass index as confounders. We used PhenoScanner searches for removal of SNPs and multivariable MR analysis for assessing confounders. We observed significant causal associations between GGT level and stroke (odds ratio [OR] = 1.23, 95% CI = [1.05-1.44], and p = 0.012 with IVW; OR = 1.19, 95% CI= [1.02-1.39], and p = 0.031 with MR-PRESSO). These results were consistent after removing SNPs related to confounding factors. Similarly, in multivariable MR, GGT was associated with stroke after adjusting for confounding factors (OR = 1.30, 95% CI 1.07-1.60), p = 0.010). Because GGT level has a causal relationship with stroke, researchers should test its significance as a potential risk factor for stroke. Additional research is required to validate these results.

Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease

BackgroundHypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis. Clinical reportA 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: <115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 μg/L; reference value: 5.7–32.9 μg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 μg/L respectively). ConclusionsWe demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.