Gamma-glutamyl Transpeptidase Levels Research Articles

Differences in the prevalence of NAFLD, MAFLD, and MASLD according to changes in the nomenclature in a health check-up using MRI-derived proton density fat fraction.

International expert panels proposed new nomenclatures, metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020 and metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023, along with revised diagnostic criteria to replace non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the differences in NAFLD, MAFLD, and MASLD prevalence with changing nomenclature in a health check-up using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) to assess hepatic steatosis. We also examined the prevalence of the sub-classifications of steatotic liver disease (SLD) and the differences in characteristics among the sub-categories. We included 844 participants who underwent liver MRI-PDFF at our health check-up clinic between January 2020 and November 2022. Hepatic steatosis was defined as MRI-PDFF ≥ 5%. Participants were categorized according to NAFLD, MAFLD, MASLD, and sub-classifications of SLD. The prevalence rates of NAFLD, MAFLD, and MASLD were 25.9%, 29.5%, and 25.2%, respectively. 30.5% of the participants was categorized as SLD. The prevalence rates of the SLD sub-categories were 25.2% for MASLD, 3.7% for MASLD and alcohol-associated liver disease (MetALD), 0.1% for alcohol-associated liver disease, 1.3% for specific etiology SLD, and 0.1% for cryptogenic SLD. Compared with patients in the MASLD group, those in the MetALD group were younger, predominantly male, and exhibited higher levels of serum aspartate aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD. The separate MetALD sub-category may have clinical characteristics that differ from those of MASLD.

Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Alterations in Alanine Transaminase, Aspartate Transaminase, Gamma-Glutamyl Transpeptidase, and Creatine Kinase in Acne Patients Undergoing Isotretinoin Treatment: A Retrospective Evaluation of Laboratory Tests.

Background Isotretinoin therapy is a commonly prescribed medication by dermatologists for the treatment of acne. Regular laboratory assessments are recommended throughout the treatment period to detect any potential complications. Objectives This study aims to present the alterations in laboratory parameters throughout the course of isotretinoin therapy and identify required diagnostic testing. Methods This study involved 136 patients undergoing isotretinoin treatment at doses of 0.3-0.5 mg/kg/day, with ages ranging from 18 to 41 years. A retrospective evaluation was conducted on biomarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), creatine kinase (CK), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin, white blood cells, and thrombocytes. Levels of these parameters were analyzed prior to treatment and at the third month of treatment from the records of patients and the data were compared statistically. Moreover, the parameters of ALT, AST, CK, and GGT were graded objectively, and any alterations were noted in the patients. Results The levels of ALT, AST and GGT, along with triglycerides, total cholesterol, LDL-C, and thrombocyte levels showed significant elevation (p=0.001, p<0.001, p<0.001, p=0.001, p<0.001, p<0.001, and p=0.003, respectively). A significant decrease in HDL-C with hemoglobin was also noted (p=0.022, p=0.006, respectively). One patient (0.73%) exhibited grade 1 elevations in ALT, AST, and CK. One patient (0.73%) displayed grade 1 elevations in ALT and AST. One patient (0.73%) exhibited grade 1 elevations in AST and CK, while another patient (0.73%) had grade 1 elevationin AST and grade 3 elevationin CK. Furthermore, one patient (0.73%) had a grade 1 elevation exclusively in ALT, two patients (1.47%) had a grade 1 elevation exclusively in AST, and six patients (4.41%) exhibited a grade 1 elevation in CK only. No grade changes were observed in the GGT levels in the patients. Conclusion During isotretinoin treatment, changes in ALT and AST levels were more frequently associated with the muscle enzyme CK, while GGT levels remained unaffected. Therefore, GGT can be considered a reliable parameter for evaluating liver function in patients undergoing isotretinoin treatment.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Expression of miR-34a in Children with Progressive Familial Intrahepatic Cholestasis: A Cross-Sectional Study Based on Shiraz Pediatric Liver Cirrhosis Cohort Study

Background: Progressive familial intrahepatic cholestasis (PFIC) is a rare progressive liver disease associated with portal hypertension leading to liver failure. Most PFIC patients ultimately need liver transplantation. Therefore, identifying a precise, non-invasive biomarker for PFIC is very important. Objectives: This study aimed to investigate the microRNA-34a (miR-34a) expression levels in PFIC patients. Methods: A total of 18 PFIC patients were randomly selected from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), and 18 healthy subjects were enrolled in this study. Blood samples were obtained, and the gene expression of serum miR-34a was analyzed. Results: The results of this study showed that the serum level of miR-34a was significantly increased in PFIC patients, compared to the healthy group (P = 0.0327). However, no association was observed between miR-34a expression and clinical and laboratory findings of PFIC cases. Additionally, the results showed no correlation between miR-34a and serum levels of liver enzymes, albumin, gamma-glutamyl transpeptidase (GGT), and international normalized ratio (INR) among PFIC patients. Conclusions: miR-34a might be a beneficial, non-invasive target for PFIC diagnosis; however, further investigations with a larger population and longer duration are necessary to determine the potential of miR-34a as a diagnostic and therapeutic biomarker for PFIC.

Efficacy of traditional Chinese medicine combined with Silibinin on nonalcoholic fatty liver disease: A meta-analysis and systematic review.

The efficacy and safety of traditional Chinese medicine (TCM) combined with Silibinin in the treatment of nonalcoholic fatty liver disease (NAFLD) are still inconclusive. This meta-analysis intends to evaluation to explore the clinical efficacy and quality assessment of traditional Chinese medicine in combination with Silymarin in the treatment of NAFLD, aiming to aims to provide evidence-based data analysis for researchers and clinical practitioners involved in TCM research for NAFLD, with the hope of facilitating wider adoption and application. In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP and CBM databases from the establishment of the databases to Oct 2023. The study proposed to include studies that reported combination of TCM with Silibinin and Silibinin alone in the treatment of NAFLD, excluding studies for which full text was not available or for which data extraction was not possible; studies using animal studies; reviews and systematic reviews. All data were processed by STATA15.1 statistical software. 16 randomized controlled trials (RCTs) were included in this meta-analysis. The sample size ranged from 48 to 120, with a total of 1335 patients, including 669 in the Combined treatment group and 384 in the Silibinin group. The findings indicated that the total effective rate of combined treatment group was significantly higher than that of Silibinin alone. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), and gamma glutamyl transpeptidase (GGT) of combined treatment group were all significantly lower than that of western medicine alone. Additionally, after treating NAFLD with a combination of TCM and Silibinin, the TCM syndrome score were significantly lower than those observed with Silibinin alone. Traditional Chinese medicine in conjunction with Silibinin capsules has shown significant efficacy in the treatment of NAFLD, improving clinical symptoms, blood lipid levels, and liver function. Furthermore, it is essential to engage in multi-omics research, investigate iron death, and explore the gut microbiota as potential observational indicators for the diagnosis and inclusion criteria. Conducting more high-quality clinical experiments is necessary to further validate these findings.

The effect of dietary eugenol nano-emulsion supplementation on growth performance, serum metabolites, redox homeostasis, immunity, and pro-inflammatory responses of growing rabbits under heat stress.

Heat stress (HS) is a main abiotic stress factor for the health and welfare of animals. Recently, the use of nano-emulsion essential oils exhibited a promising approach to mitigate the detrimental impacts of abiotic and biotic stresses, ultimately contributing to the global aim of sustainable livestock production. The current study was piloted to assess the impact of eugenol nano-emulsion (EUGN) supplementation on growth performance, serum metabolites, redox homeostasis, immune response, and pro-inflammatory reactions in growing rabbits exposed to HS. A total of 100 male weaning rabbits aged 35 days were divided into 4 treatments. Rabbits were fed the diet with EUGN at different concentrations: 0 (control group; EUGN0), 50 (EUGN50), 100 (EUGN100), and 150 (EUGN150) mg/kg diet for 8 weeks under summer conditions. Dietary EUGN levels significantly improved (p < 0.05) the body weight, body weight gain, carcass weights, and improved feed conversion ratio of rabbits. EUGN supplementation significantly increased Hb, platelets, and red blood cells , while the mean corpuscular hemoglobin and eosinophils were significantly decreased compared to the control one. Compared with EUGN0 stressed rabbits, all EUGN-experimental groups had a reduction in levels of total glycerides (p < 0.01), uric acid, total bilirubin, direct bilirubin, and gamma-glutamyl transpeptidase (p < 0.01). Total antioxidant capacity and glutathione peroxidase were significantly improved by EUGN treatment when compared to the control one (p < 0.01), while the EUGN100 exhibited the greatest levels of catalase. Lipid peroxidation (malondialdehyde) was significantly decreased in EUGN-treated groups. All pro-inflammatory cytokines serum interleukin 4, Interleukin 1β, and tumor necrosis factor alpha were considerably decreased after dietary EUGN supplementation (p < 0.05). The serum concentrations of immunoglobulins (IgG and IgM) were significantly improved in rabbits of the EUGN150 group. This study shows that EUGN can be used as a novel feed additive to enhance the growth performance, immune variables, and antioxidants, and reduce the inflammatory response of growing rabbits exposed to thermal stress.

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects.

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.

Development and validation of a model for early diagnosis of biliary atresia

Background and aimsEarly diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation.MethodsInfants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses.ResultsThree predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA.ConclusionA simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

BackgroundPrevious studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear.MethodsIn this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL.ResultsCompared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves.ConclusionGGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

Genetic polymorphisms of GGT1 gene (rs8135987, rs5751901 and rs2017869) are associated with neoadjuvant chemotherapy efficacy and toxicities in breast cancer patients

BackgroundOur previous study illustrated the predictive value of serum gamma-glutamyl transpeptidase (GGT) for neoadjuvant chemotherapy (NAC) sensitivity in breast cancer patients. In this study we aim to determine whether single nucleotide polymorphisms (SNPs) in the gamma-glutamyltransferase 1 (GGT1) gene are related to the NAC response and adverse events and to find out a genetic marker in predicting NAC sensitivity.MethodsThree SNP loci (rs8135987, rs5751901, rs2017869) of GGT1 gene were selected and tested among breast cancer patients reciving NAC. Four genotype models were used in SNP analysis: co-dominant model compared AA vs. Aa vs. aa; dominant model compared AA vs. Aa + aa; recessive model compared AA + Aa vs. aa; over-dominant model compared AA + aa vs. Aa. Chi-squared test and multivariable logistic regression analysis were performed between SNP genotypes, haplotypes and pathological complete response(pCR), adverse events as well as serum GGT level.ResultsA total of 143 patients were included in the study. For SNP rs8135987 (T > C), the TC genotype in over-dominant model was inversely related with pCR (adjusted OR = 0.30, 95% CI 0.10–0.88, p = 0.029) as well as the risk of peripheral neuropathy (adjusted OR = 0.39, 95% CI 0.15–0.96, p = 0.042). The TC genotype in dominant model was significantly associated with elevated serum GGT level (OR = 3.11, 95% CI 1.07–9.02, p = 0.036). For rs2017869 (G > C), the occurrence of grade 2 or greater neutropenia (OR = 0.39, 95% CI 0.08–0.84, p = 0.025) and leukopenia (OR = 0.24, 95% CI 0.08–0.78, p = 0.017) were both significantly reduced in patients with CC genotypes. For rs5751901(T > C), the CC genotype could significantly reduce the risk of grade 2 or greater neutropenia (OR = 0.29, 95% CI 0.09–0.96, p = 0.036) and leukopenia (OR = 0.27, 95% CI 0.09–0.84, p = 0.024) in recessive model.ConclusionsThe GGT1 gene SNPs might be an independent risk factor for poor response of NAC in breast cancer patients, providng theoretical basis for further precision therapy.

Liver enzymes and the risk of stroke among the general Japanese population: a prospective cohort study.

Stroke is a major cause of morbidity and mortality. Liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), are markers of liver diseases with potential cardiovascular implications. This study aimed to investigate the prospective association between liver enzymes and stroke risk. We analyzed data from 3,379 men and 4,007 women without cardiovascular disease and registered in the Suita Study; a Japanese population-based prospective cohort study. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of stroke risk were estimated per quintiles of ALT, AST, and GGT in men and women. Within a median follow-up period of 16.7 years, 438 incident stroke events were diagnosed. In men, compared to the second quintiles, the fifth (highest) quintiles of liver enzymes showed increased stroke risks: HRs (95% CIs) = 2.07 (1.35, 3.18) in ALT, 1.66 (1.10, 2.53) in AST, and 1.76 (1.11, 2.81) in GGT. The associations did not change with cerebral infarction risk: HRs (95% CIs) = 2.09 (1.24, 3.50) in ALT, 1.84 (1.11, 3.06) in AST, and 1.74 (1.00, 3.04) in GGT, respectively. The lowest ALT, AST, and GGT quintiles tended to show increased stroke and cerebral infarction risks, yet these associations were statistically insignificant. No such associations were shown in women. Elevated ALT, AST, and GGT levels were associated with increased stroke and cerebral infarction risks among Japanese men.

[Clinical features of non-cirrhotic portal hypertension in patients with common variable immunodeficiency].

We wished to summarize the clinical features of common variable immunodeficiency (CVID) complicated by non-cirrhotic portal hypertension (NCPH) and to deepen our understanding of it. The case data of CVID complicated with NCPH admitted to Peking Union Medical College Hospital from January 1983 to May 2021 were analyzed retrospectively to summarize their clinical characteristics. Six patients with CVID combined with NCPH (three of each sex; 16-45 years) were assessed. Four patients had portal hypertension. All patients had anemia, splenomegaly, a normal serum level of albumin and transaminases, and possibly increased levels of alkaline phosphatase and gamma-glutamyl transpeptidase. Two patients were diagnosed with esophagogastric fundic varices by gastroscopy. Two patients underwent splenectomy (which improved hematologic abnormalities partially). Four patients had autoimmune disease. Two cases were diagnosed with nodular regenerative hyperplasia (NRH) upon liver biopsy. Six patients were administered intravenous immunoglobulin-G (0.4-0.6 g/kg bodyweight) once every 3-4 weeks as basic therapy. Often, CVID complicated with NCPH has: (1) The manifestations of portal hypertension as the primary symptom. (2) Autoimmune-related manifestations. Imaging can provide important diagnostic clues. The etiology may be related to hepatic NRH and splenomegaly due to recurrent infections.

Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B.

Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients. CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727-0.803) and 0.766 (95% CI: 0.711-0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA. A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.

E19 Gamma-glutamyl transpeptidase level is correlated with disease activity in oligoarticular and polyarticular Juvenile idiopathic arthritis

Abstract Introduction Gamma-glutamyl transpeptidase (GGT) level was found to be correlated with disease activity indexes in rheumatoid arthritis [1]. This association was not yet investigated in children with oligoarticular and polyarticular Juvenile idiopathic arthritis (JIA). Objectives The present study aims to investigate the correlation between GGT level and disease-related parameters in oligoarticular and polyarticular JIA. Methods We performed a retrospective study including patients with oligoarticular and polyarticular JIA responding to the 2001 International League of Associations for Rheumatology (ILAR) classification. Sociodemographic, disease-related parameters (age of onset, disease duration, patient global assessment (PGA), Pain Visual Analogue Scale (VAS), C-Reactive protein (CRP) level, Erythrocyte Sedimentation Rate (ESR), disease activity assessed using the Juvenile Arthritis Disease Activity Score (JADAS) based on ESR), and GGT level were collected. Continuous variables were expressed with median and Interquartile range (IQR). Spearman correlation was used to assess the association between GGT levels and disease-related data. Results Eleven patients were included with a median age of 12 (IQR: 10–15) years and 8 females. Median disease duration was 4 (IQR: 4–7) years and median age of onset was 8 (IQR: 5–10) years. Five patients had oligoarticular JIA, 3 had a polyarticular with positive Rheumatoid Factor (RF) form, 2 had a polyarticular with negative RF form and one had an undifferentiated JIA. Median JADAS was 3.6 (IQR: 0–9). Median ESR, CRP, and GGT levels were 14 (10–19) mm/H, 1.8 (2–6.4) mg/l, and 14 (12–16) IU/l, respectively. A strong positive correlation was found between GGT level and JADAS (r = 0.749, P = 0.008). Level of CRP and ESR were not correlated with GGT level. Besides, patient global assessment and pain VAS were positively correlated with GGT level (r = 0.670, P = 0.049; r = 0.814, P = 0.014, respectively). No correlation was found between GGT level and disease duration and number of tender or swollen joints. Conclusion The GGT level was significantly higher in patients with more active disease, higher pain, and global assessment. This suggests that GGT level can be used as a marker of disease activity as in JIA. References 1 Vergneault H, Vandebeuque E, Codullo V, Allanore Y, Avouac J. Disease Activity Score-28 using γGT permits a dual evaluation of joint activity and cardiovascular risk. J Rheumatol 2020.

The Association of Nonalcoholic Fatty Liver Disease With Neutrophil-to-Lymphocyte Ratio and Neutrophil-Percentage-to-Albumin Ratio.

Background and objective Nonalcoholic fatty liver disease (NAFLD)is closely linked to metabolic syndrome, leading to consequences related to dyslipidemia, endothelial dysfunction, type 2 diabetes, and obesity. Due to a limited understanding of the factors contributing to the progression of NAFLD, predicting clinical outcomes in patients remains challenging. In light of this, this study aimed to evaluate the association between the occurrence of NAFLD and the neutrophil-percentage-to-albumin ratio (NPAR) as well as the neutrophil-to-lymphocyte ratio (NLR). Methods A total of 115 adult patients (mean age: 58 ± 12.5 years; 55.65% male) who underwent abdominal non-contrast-enhancedCT scans were included in the study. The analysis of CTscans was conducted to assess the attenuation values of liver parenchyma. Results There was astatistically significant difference in terms of gamma-glutamyl transpeptidase (GGT), triglyceride (TG), albumin, and NPARbetween individuals with and without hepatic steatosis (GGT p<0.0001, TG p=0.0006, albumin p<0.0001, NPAR p=0.001). However, NLR values between the two groups did not show any statistical differences. NPAR (r=-0.27, p=0.0029) had a weak inverse correlation with liverattenuation value,which is expressed in Hounsfield units (HU). Conclusions Significant differences were observed in GGT, TG, albumin, and NPAR levels between individuals with and without hepatic steatosis. An inverse correlation between NPAR and liver attenuation values was also observed.

Statins on nonalcoholic fatty liver disease: A systematic review and meta-analysis of 14 RCTs.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising rapidly in the world. Our aim is to investigate the efficacy and safety of statins in the treatment of NAFLD. This study was conducted by searching The National Library of Medicine, Cochrane Library, China National Knowledge Infrastructure, Web of Science, and Wanfang Data Knowledge Service Platform databases. Literature data are expressed as mean difference (MD) and 95% confidence intervals (CIs) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used. Fourteen studies are selected for this meta-analysis, which includes totally 534 patients in the treatment group and 527 patients in the control group. As a result, 5 studies show that the total effective rate of the treatment group is 17% higher than that of the control group (Z = 2.11, relative risk = 1.17, 95% CI: [1.01-1.35]). Twelve studies show that alanine aminotransferase levels of the experimental group are lower than that of the control group (Z = 2.63, P = .009, MD = -5.53, 95% CI: [-9.64 to -1.41]). Eleven studies show that aspartate transaminase levels of the experimental group are lower than that of the control group (Z = 2.01, P = .04, MD = -3.43, 95% CI: [-6.77 to -0.08]). Six studies show that alkaline phosphatase levels of the experimental group are lower than that of the control group (Z = 0.79, P = .43, MD = -3.46, 95% CI: [-12.08 to 5.16]). Eight studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group (Z = 2.04, P = .04, MD = -4.05, 95% CI: [-7.96 to -0.15]). Thirteen studies show that triglyceride levels of the experimental group are lower than that of the control group (Z = 4.15, P < .0001, MD = -0.94, 95% CI: [-1.39 to -0.50]). Eleven studies show that the total cholesterol levels of the experimental group are lower than that of the control group (Z = 5.42, P < .00001, MD = -1.51, 95% CI: [-2.05 to -0.96]). Seven studies show that low-density lipoprotein-cholesterol levels of the experimental group are lower than that of the control group (Z = 5.00, P < .00001, MD = -0.85, 95% CI: [-1.18 to -0.52]). Statins can significantly reduce liver biochemical indicators in patients with NAFLD.

Predictive model of persistent choledocholithiasis in patients with acute biliary pancreatitis.

Choledocholithiasis causing acute biliary pancreatitis (ABP) may migrate to the duodenum or persist in the common bile duct (CBD). We developed a model for predicting persistent choledocholithiasis (PC) in patients with ABP. This retrospective cohort study included 204 patients, age ≥18 years (mean age: 73 years, 65.7% women), admitted for ABP in 2013-2018, with at least a magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and/or endoscopic retrograde cholangiopancreatography (ERCP). Epidemiological, analytical, imaging, and endoscopic variables were compared between patients with and without PC. Multivariate logistic regression analyses were performed to develop a predictive model of PC. Patients underwent MRCP (n=145, 71.1), MRCP and ERCP (n=44, 21.56%), EUS and ERCP (n=1, 0.49%), or ERCP (n=14, 6.86%). PC was detected in 49 patients (24%). PC was strongly associated with CBD dilation, detected in the emergency ultrasound (p<0.001; OR=27; 95% CI: 5.8-185.5), increased blood levels of gamma glutamyl transpeptidase, detected at 72h (p=0.008; OR=3.4; 95% CI: 1.5-8.9); and biliary sludge in the gallbladder (p=0.008; OR=0.03; 95% CI: 0.001-0.3). The predictive model showed a validated area under the curve (AUC) of 0.858 for detecting PC in patients with ABP. A nomogram was developed based on model results. The predictive model was highly effective in detecting PC in patients with ABP. Therefore, this model could be useful in clinical practice.

AN EXPERIMENTAL STUDY ON ALBINO RATS TO COMPARE THE HEPATOPROTECTIVE EFFECT OF ORALLY ADMINISTERED DL-METHIONINE AND N-ACETYLCYSTEINE ON THE LIVER INJURY CAUSED BY POSITIVE CONTROL DRUG DICLOFENAC SODIUM

Introduction: Liver, main organ for biotransformation of drugs, during which most of the drugs which are lipophilic in nature are made hydrophilic by the biochemical processes in the liver cells resulting into water-soluble products which get excreted in urine or bile. Adverse drug reactions (ADRs) pertaining to liver, can be of mainly two types, predictable or dose dependent and idiosyncratic. To counter the oxidative stress and cellular damage, several antioxidant enzymes have been developed including superoxide dismutase (SOD), Glutathione peroxidase and catalase, that detoxify the reactive oxygen species and the cells contained endogenous antioxidants that scavenge the free radicals and reduces the cellular damage of which glutathione plays a major role. Synthesis of glutathione is regulated at the substrate level by cysteine, which is synthesized from homocysteine via the trans-sulfuration pathway N-Acetylcysteine used as a specific drug in the treatment of Paracetamol overdose, serves as a prodrug to L-Cysteine, which is a precursor to the antioxidant Glutathione. L-methionine, a precursor of L-cysteine, which is considered to have antioxidant activity, is found to be a precursor to glutathione as well. Methionine is particularly important in opposing the toxicity of free radicals generated by various toxins. Hence, supplementation of the same has been proposed to have a greater role in reducing the toxic effect on liver. The aim was to study the comparative hepatoprotective effect of orally administered DL-Methionine and N-Acetylcysteine on the liver injury induced by positive control Diclofenac Sodium. Materials and Methods: The healthy albino rats were grouped for the experimental study, in various groups (n=6). After overnight fasting, rats belonging to Group I Vehicle treated Group (n=6) were administered Distilled Water 10 ml/kg orally Group II to V were administered single oral dose concomitantly with Diclofenac sodium (96 mg/kg &amp; 240 mg/kg p.o.) and DL-Methionine (700 mg/kg p.o. &amp; 1400 mg/kg p.o.) respectively. Group VI and VII were administered single oral dose concomitantly with Diclofenac sodium (96 mg/kg &amp; 240 mg/kg p.o.) and N-Acetylcysteine 450 mg/kg p.o., respectively. Serum samples from each rats were collected after 24-hours of post-treatment, to study the comparative effects of DL-Methionine and N-Acetylcysteine on the liver injury induced by positive control Diclofenac Sodium through Haemato-biochemical changes. Results: The vehicle-treated group showed no significant alteration in the level of liver function tests and liver morphology. On concomitant administration of DL-Methionine 700 mg/kg with Diclofenac sodium 96 mg/kg and 240 mg/kg it was observed that there occurred significant reduction (p &lt; 0.001) in the serum SGOT and SGPT levels as compared to control and positive control group. The hepatoprotective effect of DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg on concomitant administration with positive control drug Diclofenac sodium 96 mg/kg were compared for their effect on serum SGPT levels and was observed that there was no statistically significant decrease in the levels of SGPT when compared between the two groups of hepatoprotective agents. The hepatoprotective effect of DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg on concomitant administration with positive control drug Diclofenac sodium 240 mg/kg, were compared for their effect on serum SGPT levels. It was observed that there was a significant reduction (p &lt;0.05) in SGPT levels, with DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg. However, in both the doses of DL-Methionine, there were no statistically significant changes in the Total Serum Bilirubin, serum Alkaline Phosphatase &amp; serum Gamma-Glutamyl Transpeptidase (GGTP) levels. Conclusion: We have compared for the effectiveness of DL-Methionine and N-Acetylcysteine for their hepatoprotective effect against Diclofenac-induced hepatotoxicity, where we have observed, both DL-Methionine and N-Acetylcysteine reduces the serum transaminases levels, that were elevated due to the hepatotoxic effect of diclofenac sodium. However, there was no much of a difference of hepatoprotective effect of both DL-Methionine and N-Acetylcysteine. In summary, our present study reinforced the concept that hepatotoxicity induced by drug can be protected by administering NAC even in cases of non-paracetamol induced liver injury.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

To the Editor: Autoimmune liver disease is a chronic immune-mediated liver disease. The term “overlap syndrome” (OS) is used to describe the conditions in which patients simultaneously or consecutively present with features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis and autoimmune hepatitis (AIH).[1] PBC-AIH OS is described most frequently,[2] with a prevalence of approximately 8% to 20% in adult patients with either pure PBC or AIH. A recent study revealed that the inpatient outcomes and survival of PBC-AIH OS patients were significantly worse and shorter than those of patients with either pure PBC or AIH, respectively.[3] At present, there is no consensus regarding which specific risk factors can predict poor response in PBC-AIH OS. To identify the baseline clinical characteristics and immunological markers for predicting non-response in PBC-AIH OS, we evaluated the survival and factors that were significantly associated with response and systematically assessed cytokine perturbations in the periphery and liver in 134 PBC-AIH OS patients at West China Hospital of Sichuan University from October 2013 to January 2021. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University (No. 2013-221). Informed consent was obtained from each patient. PBC patients were diagnosed with PBC-AIH OS according to the Paris criteria and/or PBC patients with distinct AIH features, which included sustained high levels of serum transaminase >3-fold above the upper limit of normal (ULN) for at least 3 months and/or serum immunoglobulin G (IgG) level >1.3-fold above the ULN and/or histological features of moderate to severe interface hepatitis. When patients met two or more of these diagnostic criteria, PBC-AIH OS was conservatively diagnosed. Patients were treated with ursodeoxycholic acid (UDCA) plus methylprednisolone alone or in combination with azathioprine or other immunosuppressants according to the guidelines. The criteria to evaluate the response were complete biochemical response (CBR) or partial biochemical response (PBR) within 6 months after immunosuppression therapy. CBR was defined as normal serum transaminase and IgG levels, while PBR was referred to as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2 × ULN. Anything less than a CBR and PBR was considered a non-responder. Kaplan–Meier survival curves were used to compare the prognosis between the two groups. Eleven cytokines were detected in serum from some patients (27 responders and 35 non-responders) in the two groups by Luminex assays (AliveX Biotech, Shanghai, China). Liver tissues were collected from six random patients in the two groups, and real-time quantitative polymerase chain reaction (qPCR) was conducted to determine the mRNA levels of those cytokines in liver tissues. Supplementary Table 1, https://links.lww.com/CM9/B120 summarizes the baseline demographic data of all enrolled patients. The histopathological features of PBC-AIH OS were presented in Supplementary Figure 1, https://links.lww.com/CM9/B120. A total of 48.5% of patients did not respond to treatment [Supplementary Figure 2A, https://links.lww.com/CM9/B120]. CBR was achieved in only 41 (30.6%) patients, while 28 (20.9%) patients obtained PBR. The median follow-ups were 30.0 and 24.0 months for the responders and non-responders, respectively. Kaplan–Meier analysis revealed that responders had a significantly higher liver-related adverse event-free survival rate than non-responders (log-rank: P < 0.001) [Supplementary Figure 2B, https://links.lww.com/CM9/B120]. Non-responders were more prone to jaundice than responders (P = 0.038) [Supplementary Table 2, https://links.lww.com/CM9/B120]. Univariate analysis revealed that total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and cholesterol (CHOL) levels were higher in non-responders than in responders (all P < 0.05), and the frequency of anti-mitochondrial antibody (AMA) positivity was higher in non-responders than in responders (P = 0.007). In addition, the frequency of cirrhosis was higher in the non-responders than in the responders (P = 0.001) [Supplementary Table 3, https://links.lww.com/CM9/B120]. There was no difference between the hallmarks of AIH histology that were recorded, but it is important to note that ductopenia, as a typical change in PBC, was seen more often in non-responders than in responders (P < 0.001). No significant differences were observed for the fibrosis stage and activity grade between the two groups [Supplementary Table 4, https://links.lww.com/CM9/B120]. In the final stepwise multivariate logistic regression analysis model, high CHOL levels, ductopenia, and the presence of cirrhosis were identified as risk factors for a poor response (all P < 0.01) [Supplementary Table 5, https://links.lww.com/CM9/B120]. Serum interleukin-33 (IL-33), interferon-γ (IFN-γ), and IL-21 levels in the non-response group were higher than those in the responders (all P < 0.05) [Supplementary Figure 2C, https://links.lww.com/CM9/B120]. Similar to the difference in serum, we observed a small but significant elevation in IL-33 and IFN-γ levels in the liver in the non-responders (both P < 0.05) [Supplementary Figure 2D, https://links.lww.com/CM9/B120]. Studies have already linked hypercholesterolemia to poor prognosis in patients with cholestasis, and in the present study, higher baseline serum CHOL levels were found to be associated with non-response. As CHOL-lowering medications are recommended on a case-by-case basis in a subgroup of PBC patients with metabolic syndrome,[4] our finding is encouraging for the potency of CHOL-lowering therapy in PBC-AIH OS patients with poor response, such as pravastatin, which is metabolized in a two-channel fashion, which may be efficient and safe in this setting. The present study shows that baseline ductopenia was more common in the poor response group. Ductopenia refers to evident bile duct destruction, which is not a typical feature of AIH and then signs the consideration of PBC or variant syndrome, implying that a histologically predominant PBC feature may help predict a poor response to immunosuppressive therapy. In our study, cirrhosis was prevalent and was significantly associated with a poor response, which was consistent with those of Ozaslan et al,[5] as they found that the presence of advanced fibrosis was associated with an incomplete response to the combination of UDCA and immunosuppressants. Our findings showed that the baseline levels of serum IL-33, IL-21, and IFN-γ at baseline were elevated in the poor-response group, and the mRNA levels of IL-33 and IFN-γ at diagnosis were also upregulated in their liver tissues, indicating that cytokine-based therapies may be a new therapeutic target in this group of patients. This study describes the largest cohort of patients with PBC-AIH OS to date and describes the treatment response and outcomes. A limitation of this study is that it was conducted in a large single-center and was a retrospective analysis of prospectively documented data; however, prospective interventional therapeutic trials may not be expected in the foreseeable future due to the low prevalence of this condition. In conclusion, the current results suggest that nearly half of patients with PBC-AIH OS had a poor response to immunosuppressive therapy, with a worse prognosis than responders. Features of high CHOL level, ductopenia, and the presence of cirrhosis at baseline appear to predict a poor response to immunosuppressive therapy. Additionally, higher baseline IL-33 and IFN-γ levels in serum may help identify patients who need timely intervention and second-line immunosuppressive agents. Acknowledgements We would like to thank the patients who enrolled in the study and the staff and postgraduate students. Funding This study was supported by grants from the National Natural Science Foundation of China (No. 82100552), the Science and Technology Department of Sichuan Province of China (No. 2021YJ0468), and the PostDoctor Research Project, West China Hospital, Sichuan University (No. 2020HXBH085). Conflicts of interest None.