Higher Gamma-glutamyl Transferase Research Articles

The effectiveness of liver function tests in the prediction of mortality in patients with COVID-19.

To evaluate the impact of liver function test abnormalities on mortality in critically ill coronavirus disease- 2019 patients. The single-centre, retrospective study was conducted at the Department of Anaesthesiology and Reanimation, Mersin City Training and Research Hospital, Turkiye, and comprised data from March 2020 to January 2022 of patients with positive real-time reverse transcription polymerase chain reaction test on nasopharyngeal swab sample for coronavirus disease-2019. Comorbidities, demographic data, admission to and discharge from the intensive care unit, Acute Physiology and Chronic Health Evaluation II scores, complete blood count on the first and second day of hospitalisation, coagulation parameters, biochemical analysis, 7-day, 28-day and total mortality of the patients in the intensive care unit were recorded. The patients were then divided into groups, with Group 1 having patients with normal liver enzymes, Group 2 having patients with abnormal liver enzymes, and Group 3 having patients with liver damage. Data was analysed using SPSS 20. Of the 940 subjects, 587(62.4) were males and 353(37.6) were females. The overall mean age of the patients was 67.11±16.65 years. There were 395(42%) patients in Group 1, 534(56.8%) in Group 2 and 11(1.2%) in Group 3. Gamma-glutamyl transferase-1s, aspartate aminotransferase-2nd and albumin-2nd were significant predictors of mortality (p<0.05). High gamma-glutamyl transferase, aspartate aminotransferase and low albumin levels in critically ill coronavirus disease-2019 patients could be considered indicators of high mortality rate.

Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.

In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50U/L were defined as improved (n=33). Patients with GGT levels ≥50U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6mg/dL), AST (22 vs. 28U/L), and ALT (18 vs. 27U/L) levels than nonimproved cases (n=29, p<0.05), and the change in platelet count (-0.5 vs. -3.0×10-4/μL) was significantly lower in the latter (p=0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50U/L compared to cases not treated with UDCA (18.2%, p=0.04). In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.

Renal Assessment in the Setting of Pediatric Living Related Liver Transplantation

Abstract Background Liver transplantation in the pediatric age group has become the last resort and yet the preferred option for many end stage liver disorders. This field shows a great improvement and is considered a breakthrough achievement for previously fatal liver diseases. Renal functions are not thoroughly studied in pediatric patients undergoing liver transplantation. Aim of the Work To determine the prevalence and risk factors of renal dysfunction among pediatric living related liver transplantation (LRLT). Patients and Methods This was a cross sectional retrospective and prospective cohort study in which a pilot study for a six-month duration is estimating the incidence of renal dysfunction among LRLT. A total of 40 patients were enrolled during the duration of the study from Ain Shams University, pediatric hospital and Dr. Yassin Abdel Ghaffar charity center for liver disease and research. Full history and clinical examination was performed as well as base line investigations preoperatively including: Serum Creatinine, Urea, Na, K, PO4, Ca, corrected creatinine clearance and urine analysis. Post-operative assessment was done to same parameters in addition to: Serum Mg, Cl, HCO, uric acid, drug trough level of used immunosuppressive drugs, 24 hours’ urinary proteins, and 24 hours’ assessment of electrolytes (Na, K, Ca, PO4, HCO3) in case of lowered serum levels. Moreover, pre and postoperative pelviabdominal U/S to check kidney status (size, echogenicity, RI of renal arteries) was assessed. Results Forty patients were analyzed of which 70% of the patients were males. The mean age at transplantation was 6.84±3.3 years. The commonest diagnosis of the studied group was high gamma-glutamyl transferase (GGT) cholestasis (35%) followed by Biliary atresia (22.5%). Of the enrolled patients, 50% were CHILD-B score, the median of the CHILD Score prior to transplantation was 8 and the median of the PELD score was 7.4. 87.5% of the patients had normal urine analysis, and normal proteinuria in 100% of the patients. The postoperative laboratory investigations were within the normal ranges. Mg was low in 67% of patients while Ca was low in 42.5%.The mean of creatinine, K and Ca levels are significantly elevated after LT (P &amp;lt; 0.05). After a mean duration since transplantation of 4 years, we found that 82.5% of our patients were CKD G1. S. creatinine was positively correlated with the patient age, duration of transplantation, s. uric acid, and average Fk level over the past year(P &amp;lt; 0.05 for all). Conclusion Renal dysfunction is a common, yet may be an underestimated, problem after pediatric liver transplant. Renal impairment was limited in our patients probably due to favorable perioperative conditions. Our pediatric recipients require mandatory and planned nephrologic evaluation to early detect any renal impairment which may develop into an end-stage renal disease and eventually increase the patient mortality rate. Further studies with larger cohort of patients and more advanced methods of assessment of renal functions are recommended.

Iron Metabolism in Pediatric Living related Liver Transplantation

Abstract Introduction Iron deficiency is a frequent cause of anemia in liver transplant recipients, especially children. Rejection and infection are incriminated causes for occurrence of anemia after liver transplantation (LR). Aim of the Work We aimed to assess iron homeostasis in children who have undergone living related LT (LRLT) and its correlation with occurrence of rejection and infection. Patients and Methods The study was conducted on 35 children who have undergone LRLT. The patient characteristics, frequency of infection and rejection episodes, laboratory investigations including complete blood picture (CBC) and Iron profile (total iron binding capacity (TIBC),serum iron and ferritin) during the patient follow up visits were reported. Results Males were 68.58% of the studied patients and females were 31.42%. Their ages ranged from 1.3-15 years at time of LT with mean (SD) of 7.18 (3.8)years. The mean (SD) duration since LT was 4.83 (4.2) years. The commonest indication to LT was highgamma-glutamyl transferase (GGT) cholestasis (34.7%) followed by biliary atresia (21.7 %). Thirteen percent of patients had low hemoglobin (Hb) of whom 4.3% had normocytic normochromic anemia and 8.7% had microcytic hypochromic anemia. Serum iron was normal in 79.6% of patients and low in 20.4%, and ferritin was normal in 58.7% of patients and low in 41.3% while TIBC was normal in 82.6% of patients and low in 17.4%. Only serum iron showed significant negative correlation with white blood cells (WBCs) (P &amp;lt; 0.05). The iron parameters levels were not different in patients with no rejection or only one attack of rejection and the patients with multiple rejection episodes (P &amp;gt; 0.05). Conclusion Anemia is a reported complication after pediatric LT. Further studies are needed to assess the long term effect of post-LT anemia on patient outcome after LT.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

BackgroundTo assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.MethodsData of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.ResultsAfter a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15–1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15–1.20), 1.20 (1.18–1.22), 1.69 (1.47–1.93), 1.06 (1.06–1.07), 1.08 (1.07–1.09), 1.81 (1.37–2.39), or 0.29 (0.18–0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43–5.48), 4.03 (2.69–6.03), 1.97 (1.40–2.77), 4.69 (2.98–7.37), 2.51 (1.75–3.59), 2.09 (1.51–2.89), or 2.22 (1.55–3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19–1.41).ConclusionsUnhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Lower muscular strength is associated with greater liver fat content and higher serum liver enzymes-"The Sedentary's Liver" The Study of Health in Pomerania.

We investigated the associations of low handgrip strength (HGS, i.e., a marker of muscular fitness) with liver fat content (LFC) and serum liver enzymes in a population-based setting. We used data from 2700 participants (51.7% women), aged 21-90years, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-START-2 and SHIP-TREND-0). Cross-sectional, multivariable adjusted regression models were performed to examine the associations of HGS with LFC, measured by magnetic resonance imaging and serum liver enzymes. We found significant inverse associations of HGS with both LFC and serum liver enzymes. Specifically, a 10-kg lower HGS was associated with a 0.59% (95% confidence interval [CI]: 0.24-0.94; p=0.001) higher LFC, a 0.051µkatal/L (95% CI: 0.005-0.097; p=0.031) higher gamma-glutamyltransferase (GGT) concentration and a 0.010µkatal/L (95% CI: 0.001-0.020; p=0.023) higher aspartate aminotransferase (AST) concentration. The adjusted odds-ratio for prevalent hepatic steatosis (defined by a MRI-PDFF ≥5.1%) per 10-kg lower HGS was 1.21 (95% CI: 1.04-1.40; p=0.014). When considering only obese individuals, those with low HGS had a 1.58% (95% CI: 0.18-2.98; p=0.027) higher mean LFC and higher chance of prevalent hepatic steatosis (adjusted OR 1.74, 95% CI: 1.15-2.62; p=0.009) compared to individuals with high HGS. We found similar associations in individuals with overweight, but not in those with normal weight. Lower HGS was strongly associated with both higher LFC and higher serum GGT and AST concentrations. Future studies might clarify whether these findings reflect adverse effects of a sedentary lifestyle or aging on the liver.

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 (&lt;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.