scholarly journals Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110553
Author(s):  
Yadi Li ◽  
Yan Yang ◽  
Yufang Li ◽  
Ping Zhang ◽  
Gaiying Ge ◽  
...  

Objective To evaluate the utility of Golgi protein 73 (GP73) in the diagnosis of non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) staging. Methods Ninety-one patients with non-alcoholic fatty liver disease (NAFLD) were allocated to NAFL (n = 46) and NASH (n = 45) groups according to their NAFLD activity score (NAS), and there were 30 healthy controls. Serum GP73 was measured by ELISA, GP73 protein expression was evaluated using immunohistochemistry, and FibroScan was used to determine liver hardness. Results The serum GP73 concentrations of the NAFL and NASH groups were significantly higher than those of controls. GP73 expression in the liver of the patients gradually progressed from absent or low to moderate or high. Serum GP73 positively correlated with liver expression, and the serum and liver GP73 of the patients positively correlated with FibroScan value and HF stage. There was a strong positive correlation of the combination of alanine aminotransferase, gamma glutamyl transferase and GP73 with NASH. The combination of serum GP73 and FibroScan value was found to predict NASH (NAS > 4) and advanced HF (stage ≥2) in patients with NAFLD using receiver operating characteristic analysis. Conclusion Serum GP73 may be useful in the diagnosis of NASH and the staging of HF.

2020 ◽  
pp. jmedgenet-2019-106706
Author(s):  
Weisha Luan ◽  
Chen-Zhi Hao ◽  
Jia-Qi Li ◽  
Qing Wei ◽  
Jing-Yu Gong ◽  
...  

BackgroundFor many children with intrahepatic cholestasis and high-serum gamma-glutamyl transferase (GGT) activity, a genetic aetiology of hepatobiliary disease remains undefined. We sought to identify novel genes mutated in children with idiopathic high-GGT intrahepatic cholestasis, with clinical, histopathological and functional correlations.MethodsWe assembled a cohort of 25 children with undiagnosed high-GGT cholestasis and without clinical features of biliary-tract infection or radiological features of choledochal malformation, sclerosing cholangitis or cholelithiasis. Mutations were identified through whole-exome sequencing and targeted Sanger sequencing. We reviewed histopathological findings and assessed phenotypical effects of ZFYVE19 deficiency in cultured cells by immunofluorescence microscopy.ResultsNine Han Chinese children harboured biallelic, predictedly complete loss-of-function pathogenic mutations in ZFYVE19 (c.314C>G, p.S105X; c.379C>T, p.Q127X; c.514C>T, p.R172X; c.547C>T, p.R183X; c.226A>G, p.M76V). All had portal hypertension and, at liver biopsy, histopathological features of the ductal plate malformation (DPM)/congenital hepatic fibrosis (CHF). Four children required liver transplantation for recurrent gastrointestinal haemorrhage. DPM/CHF was confirmed at hepatectomy, with sclerosing small-duct cholangitis. Immunostaining for two primary-cilium axonemal proteins found expression that was deficient intraluminally and ectopic within cholangiocyte cytoplasm. ZFYVE19 depletion in cultured cells yielded abnormalities of centriole and axoneme.ConclusionBiallelic ZFYVE19 mutations can lead to high-GGT cholestasis and DPM/CHF in vivo. In vitro, they can lead to centriolar and axonemal abnormalities. These observations indicate that mutation in ZFYVE19 results, through as yet undefined mechanisms, in a ciliopathy.


Author(s):  
Amit Kumar Meena ◽  
Sonali Sharma ◽  
Barkha Gupta ◽  
Asrar Ahmed

Introduction: The increased prevalence of overweight, obesity, and metabolic syndrome has revealed that liver enzymes have a potential role as determinants of metabolic conditions such as, hyperlipidemia, and Cardiovascular Disease (CVD). Aim: The study aimed to investigate the correlation between liver enzymes with anthropometric indices of obesity and lipid profile in different obese phenotypes at a tertiary care. Materials and Methods: The present observational study was conducted on a total of 180 obese participants of either gender in the age group 18-59 years from December 2018 to May 2019. These were further divided into two phenotypic groups viz., Metabolically Healthy Obese (MHO group; n=90) and Metabolically Unhealthy Obese (MUHO group; n=90) according to NCEP ATP III criteria.Traditional cardiovascular risk factors were evaluated in the study participants through anthropometric viz., Body Mass Index (BMI), Waist Circumference (WC), Hip Circumference (HC), waist–hip ratio (WHR), blood pressure and biochemical investigations i.e., serum glucose, lipid profile and liver enzymes. Data was analysed by using Microsoft excel software. Results: Among 180 obese participants, 76 were males and 104 females with mean age 40.42±10.84 years. In MUHO phenotype, Gamma Glutamyl Transferase (GGT) showed a strong positive correlation with BMI (r=0.413, p=0.00001), lipid parameters viz., LDL-C (r=0.3785, p=0.0001), TC (r=0.2953, p=0.0023), TG (r=0.2623, p=0.006) and negative correlation with HDL-C (-r=0.3167, p=0.001). No significant correlation was found in MHO phenotype between liver enzymes, BMI and lipid profile parameters. Conclusion: The results of this study indicated that GGT shows a strong positive correlation with traditional risk factors in MUHO participants. Thus, raised GGT may be considered as a risk marker of CVD in MUHO phenotype.


Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2316
Author(s):  
Suguru Ikeda ◽  
Takaaki Sugihara ◽  
Takuya Kihara ◽  
Yukako Matsuki ◽  
Takakazu Nagahara ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27–81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56–157 weeks). Serum triglyceride was significantly decreased by −41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by −42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), −57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and −43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia.


2021 ◽  
Vol 15 (12) ◽  
pp. 3312-3314
Author(s):  
Shagufta Khaliq ◽  
Mudassar Ali Roomi ◽  
Shaheena Naz ◽  
Komal Iqbal ◽  
Muhammad Imran Ashraf ◽  
...  

Aim: To determine and compare gamma glutamyl transferase (GGT) and fibrinogen among obese males with and without obstructive sleep apnea (OSA). Second objective was to investigate correlation between blood pressure and GGT. Methodology: Sixty-four obese males aged 20-45 years with BMI > 25kg/m2 were included by convenience sampling. The study was conducted, after obtaining ethical approval from IRB, at the Department of Physiology, Post Graduate Medical Institute, Lahore from August 2014 to May 2015. Participants having acute or chronic inflammatory conditions were excluded. Participants were screened for OSA by Berlin and STOP BANG questionnaires. Diagnosis of OSA was made by overnight portable pulse oximetry. The participants were divided into two groups. Group I had 32 obese males with OSA. Group II contained 32 obese males without OSA. After an overnight fasting of 10-12 hours blood samples were drawn. Serum fibrinogen and GGT were measured by spectrophotometer. The data was analyzed using SPSS-22. Quantitative variables were compared between the two groups by Mann-Whitney U test. Spearman correlation was used to correlate blood pressure and GGT among the participants. Results: Fibrinogen was significantly raised (p=0.015) in obese males with OSA. Systolic blood pressure (p=0.003), diastolic blood pressure (p=0.001) and mean arterial blood pressure (p<0.001) showed strong positive correlation with GGT in obese males with OSA. Conclusion: Proinflammatory, procoagulant and proatherogenic marker fibrinogen levels were significantly raised in obese otherwise healthy males with OSA. Oxidative stress marker GGT showed strong positive correlation with blood pressure in obese males with OSA. Keywords: Fibrinogen, gamma glutamyl transferase, inflammation, obstructive sleep apnea, oxidative stress


2019 ◽  
Vol 31 (5) ◽  
pp. 665-673 ◽  
Author(s):  
Maud Menard ◽  
Alexis Lecoindre ◽  
Jean-Luc Cadoré ◽  
Michèle Chevallier ◽  
Aurélie Pagnon ◽  
...  

Accurate staging of hepatic fibrosis (HF) is important for treatment and prognosis of canine chronic hepatitis. HF scores are used in human medicine to indirectly stage and monitor HF, decreasing the need for liver biopsy. We developed a canine HF score to screen for moderate or greater HF. We included 96 dogs in our study, including 5 healthy dogs. A liver biopsy for histologic examination and a biochemistry profile were performed on all dogs. The dogs were randomly split into a training set of 58 dogs and a validation set of 38 dogs. A HF score that included alanine aminotransferase, alkaline phosphatase, total bilirubin, potassium, and gamma-glutamyl transferase was developed in the training set. Model performance was confirmed using the internal validation set, and was similar to the performance in the training set. The overall sensitivity and specificity for the study group were 80% and 70% respectively, with an area under the curve of 0.80 (0.71–0.90). This HF score could be used for indirect diagnosis of canine HF when biochemistry panels are performed on the Konelab 30i (Thermo Scientific), using reagents as in our study. External validation is required to determine if the score is sufficiently robust to utilize biochemical results measured in other laboratories with different instruments and methodologies.


2019 ◽  
Vol 30 (2) ◽  
pp. 58-62
Author(s):  
Sheikh Mohammad Noor E Alam ◽  
Shahinul Alam ◽  
Dulal Chandra Das ◽  
Mamun Al Mahtab

Background: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from simple steatosis to steatohepatitis, advanced fibrosis, and end stage liver disease. Despite the high prevalence and severity of hepatic illness, NAFLD remains underdiagnosed, because of few symptoms, lack of accurate laboratory markers. Objective: To evaluate a biochemical score for diagnosing non-alcoholic steatohepatitis. Methods: An observational, cross sectional study was carried out for a period of two years in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. 43 patients of Non-alcoholic fatty liver disease (NAFLD) attending at department of Hepatology were selected and underwent for biochemical investigations and liver biopsy with NAFLD Activity Score (NAS). Results: A biochemical score (TAAG score) assigned 1 point for each parameter (fasting serum triglyceride >ULN, alanine aminotransferase >ULN, AST/ALT ratio (AAR) ≤1 and gamma-glutamyl transferase >ULN) was evaluated. TAAG score ≥3 was present in 32.5% of study population and 40% of NASH patients. It had a sensitivity of 40%, specificity 26% and AUROC 0.54. Conclusion: Biochemical scoring system comprising traditional biomarkers did not significantly predict NASH. Biopsy is the only way to estimate steatohepatitis and/or fibrosis. Bangladesh J Medicine July 2019; 30(2) : 58-62


2021 ◽  
Author(s):  
Liling Wu ◽  
Man Zhang ◽  
Haofei Hu ◽  
Qijun Wan

Abstract Background Effective and applicable predictors of non-alcoholic fatty liver disease (NAFLD) are needed for the non-obese Chinese population. We investigated whether serum gamma-glutamyl transferase (GGT) was associated with incident NAFLD in the non-obese Chinese population. Methods This was a retrospective cohort study that enrolled a total of 33153 initially NAFLD-free individuals who underwent a health examination in Wenzhou Medical Center of Wenzhou People’s Hospital from January 2010 to December 2014. We determined the relationship between GGT at enrollment and incident NAFLD during follow-up in 11906 persons. The relationship between GGT levels and incident NAFLD was analyzed using Cox regression and generalized additive models after adjustment for demographic and clinical variables. In addition, we also performed a subgroup analysis, which was explored by Cox proportional hazard models. It was stated that the data had been downloaded from the DATADRYAD website. Result Multivariable Cox regression models were used to estimate the hazard ratio (HR) for GGT with incident NAFLD after adjusted demographic and clinical variables. (HR, 1.010; 95% CI, 1.007–1.012; P < 0.001). The incident NAFLD in the highest quartile of GGT levels was 3.653 times as high (95% confidence interval, 2.915 to 4.579) as that in the lowest quartile. A non-linear relationship was firstly detected between GGT and incidence of NAFLD, which had an inflection point of GGT was 26U/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.104(1.089–1.120)and 1.001༈0.999–1.004༉, respectively. In subgroup analyses, the hazard ratio for incident NAFLD remained consistent across subgroups. Conclusion In conclusion, the GGT level in the non-obese Chinese population was statistically significantly associated with incident NAFLD. The relationship between GGT level and incident NAFLD is non-linear. When GGT level is less than 26 U/L, GGT was strong positively with incident NAFLD.


2021 ◽  
Vol 8 (7) ◽  
pp. 934
Author(s):  
Anant Parasher ◽  
Kunal Ranjan

Background: Non-alcoholic fatty liver disease (NAFLD) is a condition defined by excessive fat accumulation in the form of triglycerides (steatosis) in the liver. In recent years, an association between elevated serum uric acid concentrations and NAFLD has been reported. The aim of the study was to perform cross-sectional study to determine the association between serum uric acid levels and the levels of serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), in NAFLD patients.Methods: In this hospital-based cross-sectional study, 300 patients with diagnosed NAFLD were included during the one-year period from July 2015 to June 2016.Results: Elevation of alanine aminotransferase levels was seen in a total of 93 cases (31%) and elevation of GGT levels in NAFLD patients was seen in 112 patients out of a total of 300 (37.33%). Hyperuricemia was observed in 99 cases out of a total of 300 cases of NAFLD (33%). A significant association was observed between the two parameters.Conclusions: The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83 %) (p<0.001), and the prevalence rate increased with progressively higher serum uric acid levels (p<0.001). The relationship between rising uric acid levels with rising ALT and GGT levels in these patients was also found to be statistically significant.


2016 ◽  
Vol 71 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Svetlana Vital'evna Smirnova ◽  
Anna Aleksandrovna Barilo ◽  
Marina Viktorovna Smol'nikova

Purpose of the study. To assess the state of the hepatobiliary system in psoriasis and psoriatic arthritis in order to establish a causal relationship and to identify clinical and functional predictors of psoriatic disease progression.Methods. The study included patients with extensive psoriasis vulgaris (n = 175) from the age of 18 to 66. Divided into 3 groups: 1 – psoriasis patients with isolated skin lesions (n = 77), 2 – patients with psoriatic arthritis (n = 98), 3 – apparently healthy blood donors (n = 30), matched by sex and age. The evaluation of functional state of the hepatobiliary system was performed by analysis of the clinical and anamnestic data and by the laboratory- instrumental methods.Results. Identified predictors psoriasis: triggers (stress and nutritional factor),  increased total bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, eosinophilia, giardiasis, carriers of hepatitis C virus, and changes focal ductal formation in the liver , thickening of the walls of the gallbladder by ultrasound. Predictors of psoriatic arthritis: age over 50 years, dyspeptic complaints, the presence of hepatobiliary system diseases, the positive right hypochondrium syndrome, the clinical symptoms of chronic cholecystitis, excess body weight, high  levels of bilirubin, cholesterol and low density lipoprotein, hepatomegaly, non-alcoholic fatty liver disease.Conclusion. High activity of hepatocytes cytolysis, cholestasis, inflammation, metabolic disorders can be considered psoriatic arthritis as a severe clinical stage psoriatic disease where the hepatobiliary system, in turn, is one of the main target organs in systemic psoriatic process. Non-alcoholic fatty liver disease and chronic cholecystitis are predictors of psoriatic disease progression.


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