Higher Gamma-glutamyl Transferase Research Articles

Assessing Bone Mineral Density in Sickle Cell Disease Patients and linking it to Admission Rates: A Prospective Uni-center Study

INTRODUCTION: Sickle cell disease (SCD) is an inherited autosomal recessive disorder with bone mineral density (BMD) as a common clinical manifestation of SCD. With a prevalence of 2.6%, Saudi Arabia is among the highest incidence of SCD worldwide. The purpose of this research was to examine how SCD evolves and how it affects bone density in Saudi patients from an Eastern Province tertiary hospital. METHODS: This was an observational prospective study conducted in the tertiary care hospital among 119 SCD patients. Patients were divided into two groups: Group A – severe SCD patients requiring hospital care ≥3/year; and Group B included patients with a smooth course of SCD who did not require frequent hospitalization (<3 hospitalizations per year), with a milder course of the disease. Analysis was based on the frequency of hospitalizations with pain crises and measuring BMD. RESULTS: Of 119 patients, 73.1% had low bone density. Compared to the femur (47.9%), the spine (62.2%) had a higher prevalence of low bone density. The prevalence of low BMD did not significantly differ between the two groups (64.8 vs. 79.9%, P = 0.081). Patients with more frequent hospital visits had significantly higher Mg concentrations (2.30 vs. 0.84, P = 0.001), higher gamma-glutamyl transferase (59.44 vs. 39.49, P = 0.030), and significantly lower 25-hydroxy Vitamin D (34.82 vs. 49.48, P = 0.004). CONCLUSIONS: Patients with SCD had a generally higher prevalence of low BMD. Further research is needed to answer the proposed debate about the accuracy of DXA scanning in patients with SCD.

Liver magnetic resonance elastography and fat fraction in pediatric patients withcystic fibrosis versus healthy children.

Liver involvement is an important cause of morbidity and mortality in patients withcystic fibrosis (CF). While liver biopsy is the gold standard for demonstrating involvement, its invasiveness prompts a search for noninvasive alternatives. To evaluate liver involvement in pediatric patients with CF(versus healthy controls) using magnetic resonance (MR) elastography/spectroscopy and to correlate the imaging findings with clinical/laboratory characteristics. This was a single-center, prospective cross-sectional study conducted between April 2020 and March 2022 in patients withCF versus healthy controls. Patients with CF were divided into two subgroups: those with CF-related liver disease and those without. MR images were acquired on a 1.5-tesla machine. Kilopascal (kPa) values were derived from processing MR elastography images. MR spectroscopy was used to measure liver fat fraction, as an indication of hepatosteatosis. Groups were compared using either the Student's t test or the Mann‒Whitney U test. The chi-square test or Fisher's exact test were used to compare qualitative variables. Fifty-one patients with CF (12 ± 3.3years, 32 boys) and 24 healthy volunteers (11.1 ± 2.4years, 15 boys) were included in the study. Median liver stiffness (P=0.003) and fat fraction (P=0.03) were higher in the CF patients than in the controls. Median liver stiffness values were higher in CF patients with CF-related liver disease than in those without CF-related liver disease (P=0.002). Liver stiffness values of CF patients with high alanine aminotransferase (ALT), high gamma-glutamyl transferase, and thrombocytopenia were found to be higher than those without (P=0.004, P<0.001, P<0.001, respectively). Only the high ALT group showed a high fat fraction (P=0.002). Patients withCF had higher liver stiffness than the control group, and patients withCF-related liver disease had higher liver stiffness than both the CF patients without CF-related liver disease and the control group. Patients withCF had a higher fat fraction than the control group. Noninvasive assessment of liver involvement using MR elastography/spectroscopy can support the diagnosis of CF-related liver disease and the follow-up of patients withCF.

Sequential high-intensity focused ultrasound treatment combined with chemotherapy for inoperable pancreatic cancer: a retrospective analysis for prognostic factors and survival outcomes

Objective To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators. Methods We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second). Univariate and multivariate Cox regression analysis was used to determine the prognostic value of tumor inflammation-related serological markers. A nomogram model was established based on the identified prognostic factors. Results Univariate analysis showed that receiving the treatment regimen in HIFU-priority was a significant protective factor for overall survival (OS, p < 0.001). Tumor stage, high C-reactive protein (CRP), high gamma-glutamyl transferase(γGT) high carbohydrate antigen 125 (CA125), high neutrophil-to-lymphocyte ratio (NLR), high lymphocyte-to-monocyte ratio (LMR) and liver metastasis were significant risk factors for poor prognosis (p < 0.05). CRP combined with normal tumor marker CA125 (CRP + CA125) was associated with longer OS (p = 0.005). Multivariate analysis shows that HIFU-priority is a protective factor for OS (Hazard Ratio, HR: 0.38; 95% confidence interval(CI): 0.25-0.57), tumor stage (HR: 1.61; 95% CI: 1.12-2.31), CRP + CA125 (HR: 1.46; 95% CI: 1.02-2.08) and γGT (HR: 1.44; 95% CI: 1.04-1.98) are risk factors for OS and serve as independent prognostic factors in the nomogram. Conclusion Early application of HIFU treatment improves the OS of patients with inoperable pancreatic cancer. CRP + CA125 and γGT are independent prognostic factors.

Increased risk of ischemic stroke associated with elevated gamma-glutamyl transferase level in adult cancer survivors: a population-based cohort study

Adult cancer survivors may have an increased risk of developing ischemic stroke, potentially influenced by cancer treatment-related factors and shared risk factors with stroke. However, the association between gamma-glutamyl transferase (GGT) levels and the risk of ischemic stroke in this population remains understudied. Therefore, our study aimed to examine the relationship between GGT levels and the risk of ischemic stroke using a population-based cohort of adult cancer survivors. A population-based cohort of adult cancer survivors was derived from the National Health Insurance Service-Health Screening Cohort between 2003 and 2005 who survived after diagnosis of primary cancer and participated in the biennial national health screening program between 2009 and 2010. Cox proportional hazards model adjusted for sociodemographic factors, health status and behavior, and clinical characteristics was used to investigate the association between GGT level and ischemic stroke in adult cancer survivors. Among 3095 adult cancer survivors, 80 (2.58%) incident cases of ischemic stroke occurred over a mean follow-up of 8.2 years. Compared to the lowest GGT quartile, the hazard ratios (HRs) for ischemic stroke were 1.56 (95% CI 0.75–3.26), 2.36 (95% CI 1.12–4.99), and 2.40 (95% CI 1.05–5.46) for the second, third, and fourth sex-specific quartiles, respectively (Ptrend = 0.013). No significant effect modification was observed by sex, insurance premium, and alcohol consumption. High GGT level is associated with an increased risk of ischemic stroke in adult cancer survivors independent of sex, insurance premium, and alcohol consumption.

GAMMA GLUTAMYL TRANSFERASE LEVELS IN PATIENTS WITH ACUTE STROKE: AN ANALYTICAL STUDY

Objectives: Stroke is a significant global health issue with a major socioeconomic burden, ranking as the second leading cause of death worldwide. While stroke rates have declined in high-income countries, they have increased in low- to middle-income countries, including India. The World Health Organization defines stroke as a disturbance of cerebral function caused by vascular factors, classified as ischemic or hemorrhagic. Methods: Ischemic stroke is primarily caused by atherosclerosis in the brain’s arteries, including the proximal aorta, leading to embolus formation. Other factors contributing to stroke include arterial stenosis, coexisting thrombosis, artery-to-artery embolism, micro atheroma, lipohyalinosis, and occlusive diseases of small brain arteries. Cardiogenic embolism, often associated with atrial fibrillation, contributes to a significant proportion of ischemic strokes. Gamma-glutamyl transferase (GGT), commonly used as a marker for alcohol consumption and liver diseases, is also linked to oxidative stress, inflammation, and atherosclerosis. Elevated GGT levels are associated with various stroke risk factors. Results: GGT plays a crucial role in cellular intake of glutathione, an important antioxidant. Paradoxically, it can generate reactive oxygen species in the presence of certain metals. Studies have found a correlation between high serum GGT levels and stroke risk, potentially due to oxidative stress and atherosclerosis progression. Conclusion: Despite its primary use as an alcohol consumption marker, GGT has emerged as a potential independent biomarker for vascular diseases, including stroke. However, limited research exists on the association between GGT and acute stroke. This study aims to evaluate GGT levels in patients with acute stroke, exploring potential differences among stroke types to better understand the impact of GGT on acute stroke.

The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation.

Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.

Early bile drainage improves native liver survival in biliary atresia without cholangitis.

To explore the outcomes and related factors in children without cholangitis after Kasai portoenterostomy (KPE). We retrospectively analyzed the data of infants with type III BA who underwent KPE from June 2016 to December 2021. We compared and analyzed the difference in native liver survival (NLS) rates in different types of cholangitis. We also investigated the relationship between the absence of cholangitis and the effect of early bile drainage (EBD) as well as the related factors affecting EBD efficacy. A total of 145 children were included in this study. Among these children, 82 (56.6%, 82/145) had cholangitis, including 40 (48.8%, 40/82) with early cholangitis and 33 (40.2%, 33/82) with recurrent cholangitis. The median follow-up period was 29 months (range, 2-75 months). The NLS rates were 67.6%, 51.7%, 45.5% and 43.4% at 6 months, 1 year, 2 years and 5 years following KPE, while the NLS rates for infants without cholangitis after KPE were 68.3%, 50.8%, 46.0% and 46.0%, respectively. Higher gamma-glutamyl transferase (γ- GT) and total bile acid (TBA) before KPE were risk factors for cholangitis (P < 0.05). The NLS rate in recurrent cholangitis was significantly lower than that in occasional cholangitis (P < 0.01). Compared with the EBD-poor group, the NLS rate in the EBD-good group of infants was significantly increased (P < 0.001). EBD was significantly correlated with the occurrence and frequency of cholangitis (P < 0.05). Recurrent cholangitis was an important factor affecting NLS. For children without cholangitis after KPE, early bile drainage was better, and the NLS was longer.

The Association between Liver Enzymes and Mortality Stratified by Non-Alcoholic Fatty Liver Disease: An Analysis of NHANES III

Associations between liver enzymes or De Ritis ratio (DRR; aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) and mortality stratified by non-alcoholic fatty liver disease (NAFLD), which have rarely been analyzed in previous studies, were investigated using the National Health and Nutrition Examination Survey (NHANES) III (1988–1994). Participants without risk factors for liver diseases other than NAFLD were linked with National Death Index records through 2019 (n = 11,385) and divided into two cohorts with or without NAFLD, based on ultrasound examination. Liver enzyme concentrations were categorized into sex-specific deciles and subsequently grouped (AST and ALT: 1–3, 4–9, 10; gamma glutamyltransferase (GGT): 1–8, 9–10). DRR was categorized into tertiles. Cox proportional hazards regression models adjusted for confounders were fitted to estimate associations with mortality. Compared with low levels, high GGT and DRR in participants with and without NAFLD had significantly higher hazard ratios for all-cause mortality. Compared with intermediate concentrations, low ALT showed higher all-cause mortality in participants with and without NAFLD, whereas low AST had higher HR in participants without NAFLD and high AST in those with NAFLD. Mortality was associated with liver enzymes or DRR in participants both with and without NAFLD, indicating that the relationship is not mediated solely by hepatocellular damage.

Gamma-glutamyl transferase predicts pemafibrate treatment response in non-alcoholic fatty liver disease.

Pemafibrate, a selective peroxisome proliferator activated receptor α modulator, has been shown to improve liver function among nonalcoholic fatty liver disease (NAFLD) patients with dyslipidemia. The aim of this retrospective study is to identify predictors of pemafibrate efficacy in NAFLD patients. A total of 75 NAFLD patients with dyslipidemia who received pemafibrate twice per day for 48weeks were enrolled in this study. We used the FibroScan-aspartate aminotransferase (FAST) score as a benchmark for treatment efficacy. Median FAST score significantly decreased from 0.96 at baseline to 0.93 at week 48 (P<0.001). Significant improvements in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and triglycerides were also noted. The serum level of GGT at baseline was correlated with change in FAST score (r=-0.22, P=0.049). Changes in AST, ALT, and GGT were positively correlated with change in FAST score (r=0.71, r=0.61, and r=0.38). Multivariate analyses identified age and GGT level at baseline as significantly associated with improvement of FAST score by pemafibrate therapy (odds ratio 1.11, 1.02, respectively). Patients over 50years of age and with a GGT of 90IU/L or higher showed significantly greater improvement in the FAST score than other groups. Pemafibrate improves the FAST score of NAFLD patients with complicating dyslipidemia, especially in older patients with high GGT level. GGT is useful as an indicator of optimal treatment choice for NAFLD patients with dyslipidemia.

The Prevalence of Advanced Liver Fibrosis Among Patients With Type 2 Diabetes Mellitus: A Single-Centre Experience in Penang, Malaysia.

Type 2 diabetes mellitus (T2DM) is an important risk factor for Non-alcoholic fatty liver disease (NAFLD). It worsens the course of NAFLD. We investigated the prevalence of advanced liver fibrosis among patients with T2DM. Our secondary objectives were to describe patient demographics, to explore associated clinical factors, and to compare FIB-4 Index and liver stiffness measurement (LSM). This was a cross-sectional study on 258 patients with T2DM duration of at least 10 years. Transient elastography (FibroScan®) was performed on all subjects. Advanced liver fibrosis was diagnosed based on LSM results. The FIB-4 index formula was used. The prevalence of advanced liver fibrosis was 22.1%. Associated factors were body mass index (BMI), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), triglyceride (TG) and high-density lipoprotein (HDL) cholesterol. Independent factors were BMI and GGT (p=0.003 and p<0.001). FIB-4 index has 30.0% sensitivity, 85.0% specificity, 38.7% positive predictive value, and 79.4% negative predictive value in detecting advanced liver fibrosis by LSM criteria. Our study confirmed the high prevalence of advanced liver fibrosis among patients with long-standing T2DM. This study suggests the benefit of advanced liver fibrosis screening in patients with a minimum of 10 years of T2DM, especially those with high BMI and GGT.

An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography

We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors. A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis. Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14kPa (pretest probability, 39.4%); ≥F3, 3.53kPa (pretest probability, 24.1%); and F4, 4.45kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p<0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders. MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not. This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14kPa; advanced fibrosis, 3.53kPa; and cirrhosis, 4.45kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.

Plasma Cytokeratin-18 Fragment Level Reflects the Metabolic Phenotype in Obesity.

There is growing interest in the non-invasive identification and monitoring of the outcome of liver damage in obese patients. Plasma cytokeratin-18 (CK-18) fragment levels correlate with the magnitude of hepatocyte apoptosis and have recently been proposed to independently predict the presence of non-alcoholic steatohepatitis (NASH). The aim of the study was to analyze the associations of CK-18 with obesity and related complications: insulin resistance, impaired lipid metabolism and the secretion of hepatokines, adipokines and pro-inflammatory cytokines. The study involved 151 overweight and obese patients (BMI 25-40), without diabetes, dyslipidemia or apparent liver disease. Liver function was assessed based on alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and the fatty liver index (FLI). CK-18 M30 plasma levels, FGF-21, FGF-19 and cytokines were determined by ELISA. CK-18 values >150 U/l were accompanied by high ALT, GGT and FLI, insulin resistance, postprandial hypertriglyceridemia, elevated FGF-21 and MCP-1 and decreased adiponectin. ALT activity was the strongest independent factor influencing high CK-18 plasma levels, even after an adjustment for age, sex and BMI [β coefficient (95%CI): 0.40 (0.19-0.61)]. In conclusion, the applied CK-18 cut-off point at 150 U/l allows to distinguish between two metabolic phenotypes in obesity.

Predictors of survival in advanced oral cancers after salvage surgery with free tissue flap reconstruction

ObjectiveTo identify prognostic factors for patients with advanced persistent, recurrent, or 2nd primary oral cavity squamous cell carcinoma (OCSCC) potentially unsuitable for salvage surgery with free tissue flap (FTF) reconstruction.Materials and methodsA population-based cohort of 83 consecutive patients with advanced OCSCC who underwent salvage surgery with FTF reconstruction at a tertiary referral centre between 1990 and 2017. Retrospective uni- and multivariable analyses were performed to identify factors affecting all-cause mortality (ACM), i.e., overall survival (OS), as well as disease-specific mortality (DSM), i.e., disease-specific survival (DSS) after salvage surgery.ResultsMedian disease-free interval until recurrence was 15 months with recurrent stage I/II in 31% and III/IV in 69%. Median age at salvage surgery was 67 years (range 31–87) and the median follow-up (alive patients) 126 months. At 2, 5, and 10 years after salvage surgery, respectively, DSS rates were 61%, 44%, and 37% and OS rates 52%, 30%, and 22%. Median DSS was 26 and OS 43 months. Multivariable analysis identified recurrent clinical regional (cN-plus) disease [HR 3.57; p < .001] and elevated gamma-glutamyl transferase (GGT) [HR 3.30; p = .003] as independent pre-salvage predictors for poor OS after salvage, whereas initial cN-plus [HR 2.07; p = .039] and recurrent cN-plus disease [HR 5.14; p < .001] predicted poor DSS. Among post-salvage factors, extranodal extension according to histopathology [HR ACM 6.11; HR DSM 9.99; p < .001] as well as positive [HR ACM 4.98; DSM 7.51; p < 0.001] and narrow surgical margins [HR ACM 2.12; DSM HR 2.80; p < 0.01] emerged as independent factors for poor survival.ConclusionWhile salvage surgery with FTF reconstruction is the primary curative option for patients with advanced recurrent OCSCC, the present findings may help guide discussions with patients who have advanced recurrent regional disease and high GGT preoperatively, especially if there is a small chance of reaching surgical radicality.

Evaluation of gamma glutamyl transferase activity in sera of patients with Alzheimer’s disease

Gamma glutamyl transferase (GGT) plays a role in cellular glutathione uptake, which is an important element of antioxidant mechanisms. An increase in serum GGT is thought to be an early and sensitive marker of oxidative stress. Oxidative stress has a role in the pathogenesis of Alzheimer’s disease (AD). The aim of present study was to investigate the levels of serum Gamma glutamyl transferase (S.GGT) in samples from patient with Alzheimer’s disease.The study included 67 AD patients and 70 individuals as normal controls . Serum Gamma glutamyl transferase GGT and C-reactive protein (CRP) were determined. The study revealed that the S.GGT activity was significantly higher in patients with Alzheimer’s disease (75±2.1IU/L) than in control (healthy individuals) (25±2.1IU/L). The study was carried out in optimum pH (8.2) and optimum temperature 37ć. The results showed that There was a significant positive correlation between age and S.GGT activity in males (r=0.75); and females (r=0.72). Increase in age was significantly associated with raised GGT levels in control group and patients group. The mean serum C-reactive protein (CRP) levels were significantly (p &lt; 0.001) greater in patients group ((33.9 ± 2.3) when compared with control group (4.8±0.2). The high serum GGT concentration may play a critical role in the oxidative stress present in AD brain and, consequently, may play a central role in the pathogenesis of the disease.

Early γGT and bilirubin levels as biomarkers for regeneration and outcomes in damaged bile ducts after liver transplantation.

Early patient and allograft survival after liver transplantation (LT) depend primarily on parenchymal function, but long-term allograft success relies often on biliary-tree function. We examined parameters related to cholangiocytedamage that predict poor long-term LT outcomes after donation after brain death (DBD). Sixty bile ducts (BD)were assessed by a BD damage-score and divided into groups with "major" BD-damage (n=33) and "no relevant" damage (n=27) during static coldstorage. Patients with "major" BD damage were further investigated by measuring biliary excretion parameters in the first 14 days post-LT (followed-up for 60-months). Patients who received LT showing "major" BD damage had significantly worse long-term patient survival, versus grafts with "no relevant" damage (p=.03). When "major" BD damage developed, low bilirubin levels (p=.012) and high gamma-glutamyl transferase (GGT)/bilirubin ratio (p=.0003) were evident in the early post-LT phase (7-14 days) in patients who survived (>60 months), compared to those who did not. "High risk" patients with bile duct damage and low GGT/bilirubin ratio had significantly shorter overall survival (p<.0001). Once "major" BD damage occurs, a high GGT/bilirubin ratio in the early post-operative phase is likely indicator of liver and cholangiocyte regeneration, and thus a harbinger of good overall outcomes. "Major" BD damage without markers of regeneration identifies LT patients that could benefit from future repair therapies.

Causes and Risk Factors of Early and Late Non-Relapse Mortality after CD19 CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): A Lysa Study from the Descar-T Registry

Background CD19 CAR T-cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory diffuse large B-cell lymphomas (DLBCL). However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the non-relapse mortality (NRM) following CAR T-cells. Improving our knowledge of NRM may help guide the selection and management of patients in order to improve their outcome after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM, and identified risk factors of NRM. Methods We retrospectively analyzed patients from the DESCAR-T registry who received commercial CD19 CAR T-cells for DLBCL between July 2018 and April 2022, from 27 French centers. NRM was defined as patients who died of causes unrelated to lymphoma relapse/progression (deaths of unknown origin were excluded) within 28 days from CAR T-cell infusion (early NRM) or beyond (late NRM). Overall NRM was defined as the sum of early and late NRM. Descriptive statistics of early and overall NRM were performed and cumulative incidences calculated. Risk factors for early and overall NRM were identified by comparing the characteristics at lymphodepletion of early and overall NRM population with patients alive at day 28 post-CAR T-cell infusion or alive at 1 year following CAR-T cell infusion, respectively. Results Between July 2018 and April 2022, 977 consecutive patients registered in the DESCAR-T registry received commercial CD19 CAR T-cells for DLBCL, either axicabtagene ciloleucel (axi-cel, N=611) or tisagenlecleucel (tisa-cel, N=366). Median age was 62 years (range, 18-82), 600 (61%) patients were male, 94 (10%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) >1, 55 (5.6%) had an International Prognostic Index (IPI) >3, 459 (47%) had received ≥3 prior lines of treatment, 118 (12%) had failed a prior autologous stem cell transplant. After a median follow-up of 12.4 months, 48 (4.9%) patients had died of causes unrelated to lymphoma and defined the overall NRM population: 9 deaths (0.92% of all patients and 19% of all NRM) occurred before day 28 post-infusion (early NRM population) and 39 deaths (3.99% of all patients and 81% of all NRM) occurred beyond day 28 post-infusion (late NRM population). Causes of early NRM were cytokine release syndrome (CRS) in 5 patients, infections in 3 patients (2 bacterial sepsis and 1 bacterial pneumonia), and acute kidney failure in one patient. Risk factors for early NRM were as follows: older age (median 73 years vs 63 years, p=0.020), lower body mass index (median 22.5 vs 24.4, p=0.040), ECOG PS >1 (56% vs 13%, p=0.003), higher aspartate transaminase levels (median 68 vs 22 IU/L, p=0.012), higher total bilirubin levels (median 10 vs 6 µmol/L, p=0.035), higher LDH levels (median 408 vs 250 IU/L, p=0.019), and higher ferritin levels (median 1837 vs 480 µg/L, p=0.021). Causes of overall NRM were COVID infection in 13 patients, non-COVID infection in 12 patients (6 bacterial sepsis, 4 bacterial pneumonia, one peritonitis, one septic arthritis), CRS in 5 patients, second malignancy in 3 patients, cerebral hemorrhage in 3 patients, stroke in 2 patients, immune effector cell associated neurotoxicity (ICANS) in 2 patients, acute kidney failure in 1 patient and deaths from other causes in 7 patients. Risk factors for overall NRM were as follows: older age (median 67 years vs 63 years, p=0.003), diabetes (23% vs 10%, p=0.025), ECOG PS >1 (23% vs 5%, p<0.001), lower platelet counts (median 156 g/L vs 185 g/L, p=0.034), higher C-reactive protein levels (median 17 vs 5 mg/L, p<0.001), higher ferritin levels (median 732 vs 393 µg/L, p=0.002), and higher gamma-glutamyl transferase (GGT) levels (median 50 vs 30 IU/L, p=0.017). Conclusion To our knowledge, this is the largest study focusing on NRM after CAR T-cell therapy. NRM in patients receiving commercial CAR T-cells for DLBCL is a relatively rare event (4.9%). Most NRM occurs late (81%) and is due to infections (52%). We identified risk factors of early and overall NRM, which can be useful to select patients for CAR T-cell therapy and prevent/reduce the risk of NRM and thus ultimately improve the outcome of patients treated with CAR T-cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Demographic, clinical and laboratory predictors of hepatic steatosis and fibrosis by elastography

Giriş ve Amaç: Viral hepatitler tüm dünyada en önemli karaciğer hastalığı nedeni olma özelliğini sürdürmektedir. Bunun yanında alkolik ve nonalkolik karaciğer hastalıklarına da artan sıklıkta rastlanmaktadır. Obezite ve diyabet sıklığı ile alkol tüketimindeki artışlar, bu faktörlerin önümüzdeki yıllarda kronik karaciğer hastalıkları etiyolojisinde daha önemli olacağını düşündürmektedir. Karaciğer fibrozisi ve sonucunda gelişen siroz, kronik karaciğer hastalığının başlıca morbidite ve mortalite sebebidir. Çalışmada elastografi ile elde edilen fibrozis ve steatozis sonuçlarının biyokimyasal ve antropometrik parametrelerle olan ilişkisinin incelenmesi amaçlandı. Gereç ve Yöntem: Karadeniz Teknik Üniversitesi Tıp Fakültesi Hastanesi Gastroenteroloji Kliniği’ne başvuran ve elastografi yapılan 50 hasta çalışmaya dâhil edildi. Hastaların biyokimyasal parametreleri ve beden kitle indeksi ile elastografik steatoz ve fibrozis skorları arasındaki ilişki değerlendirildi. Elastografi kontrollü atenüasyon parametresi değerleri Li’nin skalası baz alınarak S0-S3 arasında; fibrozis/elastisite değerleri ise Petroff’un skalası baz alınarak F0-F4 arasında sınıflandırıldı. Bulgular: Çalışmaya dâhil edilen 50 hastanın 26’sı erkek, 24’ü kadındı. Ortalama yaş 49.9 ± 13.4 yıldı. Vücut kitle indeksi için ortanca değer 29.4 kg/m2 olarak saptandı. En sık eşlik eden hastalıklar hipertansiyon (n = 19, %38), diyabetes mellitus (n = 19, %38), hiperlipidemi (n = 11, %22) ve hipotiroidi (n = 7, %14) idi. Hastaların transient elastografi ile ölçülen fibrozis skorları; F0-1 %84 (n = 42), F2 %4 (n = 2), F3 %4 (n = 2 ve F4 %8 (n = 4); elastografi kontrollü atenüasyon parametresi değerleri ise S0 %61.2 (n = 30), S1 %2 (n = 1), S2 %10.2 (n = 5), S3 %6.1 (n = 3), S4 %20.4 (n = 10) şeklinde idi. Steatoz derecesi ≥ S2 olanlarda vücut kitle indeksi ve trigliserit düzeyi anlamlı olarak daha yüksekti (p &amp;lt; 0.05). Fibrozis düzeyi ≥ F2 olanlarda total kolesterol, yüksek dansiteli lipoprotein, alanin aminotransferaz ve gama glutamil transpeptidaz değerleri anlamlı olarak yüksekti (p &amp;lt; 0.05). Alıcı işlem karakteristikleri eğrisi kullanılarak yapılan analiz sonucunda steatoz derecesi ≥ S2 varlığını ön gördüren vücut kitle indeksi değerinin 29.6 kg/m2 olduğu saptanmıştır (%73.7 duyarlılık, %65.5 özgüllük, eğrinin altında kalan: 0.808, %95 güven aralığı: 0.687-0.028). Sonuç: Elastografik olarak karaciğer steatoz ve fibrozisinin belirlenmesi, hastaların rutin takiplerinde klinik durumu, prognozu ve tedavi cevabının değerlendirilmesi açısından faydalı ve etkin bir yöntemdir. Ekonomik nedenlerle uygulanamadığı durumlarda noninvaziv testlerin kullanımı ihmal edilmemelidir.

Nonalcoholic Fatty Liver Disease in Young Children with Obesity.

Background: To evaluate the prevalence of suspected nonalcoholic fatty liver disease (NAFLD) in young children with obesity and determine associated risk factors. Methods: Retrospective single-center study of children with obesity, ages 2-6 years. Suspected NAFLD was defined as an alanine aminotransferase (ALT) >30 U/L. Multivariable analyses were performed to determine predictors of elevated ALT. Results: Among 237 children 2-6 years old, 35% had elevated ALT. Multivariable analysis showed that higher BMI z score [odds ratio (OR): 1.5 confidence interval (95% CI: 1.04-1.92)] and higher gamma-glutamyl transferase (GGT) [OR: 21.3 (95% CI: 3.7-121.1)] predicted elevated ALT. Of those with ≥2 ALT levels, 38% (n = 33/86) had a persistently elevated ALT (median ALT >30 U/L). Only 7% of patients with ALT >30 U/L underwent further testing to evaluate for alternative causes of liver disease. Conclusion: Suspected NAFLD is common in young children with obesity and predicted by obesity severity and GGT. Other cardiometabolic markers were equivalent between those with normal vs. elevated ALT, suggesting NAFLD onset may precede development of comorbidities. Earlier screening will enable prompt diagnosis and intervention, which may prevent or delay the onset of cardiometabolic diseases commonly associated with NAFLD in adolescence and adulthood.

Liver-function parameters are associated with incident hypertension in a large Taiwanese population follow-up study.

Previous studies demonstrated inconsistent results regarding the association between liver function and hypertension. In addition, large cohort follow-up studies are lacking. Therefore, this longitudinal study aimed to investigate the association between liver function and incident hypertension using data from the Taiwan Biobank (TWB). We evaluated liver biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, alpha-fetoprotein (AFP), total bilirubin, and gamma-glutamyl transferase (GGT) in this study. A total of 21,293 participants without hypertension at baseline were analyzed. During the mean 3.9-year follow-up, 3002 participants developed hypertension (defined as incident hypertension). Multivariable analysis revealed that high AST (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.007; p = 0.014), high ALT (OR, 1.004; 95% CI, 1.002-1.006; p < 0.001), high albumin (OR, 1.897; 95% CI, 1.573-2.286; p < 0.001), and high GGT (OR, 1.004; 95% CI, 1.003-1.005; p < 0.001) were significantly associated with incident hypertension in all study participants. In subgroup analysis of the participants with an ALT level ≤2 times the normal limit (80 u/l) (n = 20,983), multivariable analysis demonstrated that high ALT (OR, 1.009; 95% CI, 1.005-1.012; p < 0.001) and high GGT (OR, 1.005; 95% CI, 1.003-1.006; p < 0.001) were significantly associated with incident hypertension. In conclusion, we found that elevated AST, ALT, albumin, and GGT were associated with incident hypertension in a large Taiwanese cohort. A greater understanding of potential risk factors for hypertension may help to reduce the burden of hypertension in this Taiwanese population.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.