Higher Gamma-glutamyl Transpeptidase Research Articles

Insulin resistance and hepatic steatosis in type 1 diabetes mellitus and their association with diabetic chronic complications.

The aim of this study was to evaluate insulin resistance and hepatic steatosis and their association with diabetes duration, control and chronic complications in patients with type 1 diabetes. We studied medical records of 181 consecutive hospitalized adult patients with type 1 diabetes. Estimated glucose disposal rate (eGDR), Insulin Sensitivity Score (ISS), Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) were calculated. Patients in the 1st tertile of eGDR (<4.1 mg/kg-1-min-1) and ISS (<4.8) had higher prevalence of ischemic cardiovascular disease (ICVD) (P<0.001), hepatic steatosis, higher gamma glutamyl transpeptidase, HSI, FLI compared with participants from the 2nd and 3rd tertile of eGDR and ISS. Compared with those without steatosis, patients with ultrasound-diagnosed steatosis (30.5%) had a lower ISS (4.4±1.9 vs. 6.3±2.4, P<0.001), eGDR (4.5±3.0 vs. 5.8±2.7, P=0.01), higher FLI (72.5±25.1 vs. 51.0±27.2, P<0.001), HSI (37.5±6.1 vs. 35.2±4.7, P=0.03) and prevalence of ICVD (71.7 vs. 45.7%, P=0.004) and retinopathy (69.6 vs. 52.4%, P=0.03). Factors independently associated with hepatic steatosis were only ICVD (OR=2.584, P=0.029), ISS (OR 0.148, P<0.001), aspartate aminotransferase (OR=1.025, P=0.038) and male gender (OR=2.726, P=0.016). Insulin resistance and hepatic steatosis are common in type 1 diabetes and have a significant association with ICVD, independently of diabetes duration, control and insulin doses.

Low gamma-glutamyl transpeptidase levels at presentation are associated with severity of liver illness and poor outcome in biliary atresia.

ObjectiveTo investigate the clinical features and prognosis of biliary atresia (BA) with normal or minimally elevated gamma-glutamyl transpeptidase (GGT).MethodsThe clinical data of patients with BA in our hospital between 2012 and 2017 were retrospectively studied. The patients were divided into a low-GGT group (GGT ≤ 300 IU/L) and a high-GGT group (GGT > 300 IU/L) according to the preoperative GGT level. The perioperative clinical parameters, the postoperative jaundice clearance within 6 months, and the 2-year native liver survival were compared among the groups.ResultsA total of 1,998 children were included in this study, namely, 496 in the low-GGT group and 1,502 in the high-GGT group. The ages and weights at the surgery in the low-GGT group were significantly lower than those in the high-GGT group (64.71 ± 21.35 vs. 68.64 ± 22.42 days, P = 0.001; 4.67 ± 1.03 vs. 4.89 ± 0.98 kg, P < 0.001). The levels of serum ALP, ALT, and AST in the low-GGT group were significantly higher than those in the high-GGT group before and 2 weeks after the surgery (ALP: 647.52 ± 244.10 vs. 594.14 ± 228.33 U/L, P < 0.001; ALT: 119.62 ± 97.14 vs. 96.01 ± 66.28 U/L, P < 0.001; AST: 218.00 ± 173.82 vs. 160.71 ± 96.32 U/L; P < 0.001). The INR of the low-GGT group was higher than that of the high-GGT group (1.05 ± 0.34 vs. 0.98 ± 0.20, P < 0.001), while FIB was lower than the high-GGT group (2.54 ± 0.67 vs. 2.73 ± 1.44 g/L; P = 0.006). The decreasing amplitude of TB and DB within 2 weeks after surgery in the low-GGT group was smaller than those in the high-GGT group (TB: 51.62 ± 71.22 vs. 61.67 ± 53.99 μmol/L, P = 0.003; DB: 33.22 ± 35.57 vs. 40.20 ± 35.93 μmol/L, P < 0.001). The jaundice clearance rate in the low-GGT group was significantly lower than that in the high-GGT group at 1, 3, and 6 months after surgery (17.70 vs. 26.05%; 35.17 vs. 48.58%; 38.62 vs. 54.64%, P < 0.001). In addition, the 2-year native liver survival rate in the low-GGT group was significantly lower than that of the high-GGT group (52.5 vs. 66.3%, P < 0.001 HR 1.80, 95% CI 1.38–2.33).ConclusionCompared to patients with high GGT, patients with normal or minimally elevated pre-operative GGT in BA were found to have poorer pre-operative liver function parameters, and post-operatively had lower jaundice clearance rates and worse 2-year native liver survival. This suggests a lower GGT at presentation in biliary atresia could be a sign of more severe liver injury.

Factors associated with the development of extrahepatic malignancy in patients with nonalcoholic fatty liver disease: a single-center longitudinal study.

The aim of the present study was to determine incident cases of extrahepatic malignancy in patients with nonalcoholic fatty liver disease (NAFLD) and to identify whether the factors are associated with cancer development. Between 15 January 2001 and 14 March 2021, a total of 1365 patients had been diagnosed with NAFLD were enrolled in the study. The median follow-up period was 59.5 months. The mean age was 50.9 ± 10.9 years. The female gender was predominant (57%). During the follow-up period, 62 extrahepatic malignancies and 11 hepatocellular carcinomas were identified. Of all extrahepatic malignancies, 51 were solid organ malignancies and 11 were hematological malignancies. Female breast cancer was the most frequent (25.8%), followed by thyroid cancer (19.4%), lymphoma (12.9%), and lung cancer (9.7%). In univariate and multivariable analyses, after adjusting for age and sex, the presence of diabetes and high initial baseline gamma glutamyl transpeptidase (GGT) levels were significantly associated with the development of extrahepatic malignancies [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.04-3.20, P = 0.036] and HR = 1.96, 95% CI: 1.14-3.38, P = 0.015, respectively). In 424 biopsy-proven NAFLD patients, the development of extrahepatic cancer was significantly associated with the severity of hepatic fibrosis (HR = 3.31, 95% CI: 1.36-8.07; P = 0.008). Extrahepatic malignancies are frequently seen in patients with NAFLD. Diabetes mellitus, high baseline GGT levels, and significant hepatic fibrosis are associated with the development of extrahepatic cancer in patients with NAFLD.

Case report: Unusual and extremely severe lipoprotein X-mediated hypercholesterolemia in extrahepatic pediatric cholestasis

BackgroundLipoprotein X (LpX) - mediated extremely severe hyperlipidemia is a possible feature detectable in children with syndromic paucity of intralobular bile ducts (Alagille syndrome) but rarely in other types of intra- and/or extrahepatic infantile cholestasis.Case presentationHere we report on a previously well 18-month child admitted for cholestatic jaundice and moderate hepatomegaly. Laboratory tests at entry showed conjugated hyperbilirubinemia, elevated values of serum aminotransferases, gamma-glutamyl transpeptidase (GGT) and bile acids (100 folds upper normal values). Extremely severe and ever-increasing hypercholesterolemia (total cholesterol up to 1,730 mg/dl) prompted an extensive search for causes of high GGT and/or hyperlipidemic cholestasis, including an extensive genetic liver panel (negative) and a liver biopsy showing a picture of obstructive cholangitis, biliary fibrosis, and bile duct proliferation with normal MDR3 protein expression. Results of a lipid study showed elevated values of unesterified cholesterol, phospholipids, and borderline/low apolipoprotein B, and low high-density lipoprotein-cholesterol. Chromatographic analysis of plasma lipoproteins fractions isolated by analytical ultracentrifugation revealed the presence of the anomalous lipoprotein (LpX). Magnetic resonance cholangiopancreatography and percutaneous transhepatic cholangiography showed stenosis of the confluence of the bile ducts with dilation of the intrahepatic biliary tract and failure to visualize the extrahepatic biliary tract. Surgery revealed focal fibroinflammatory stenosis of the left and right bile ducts confluence, treated with resection and bilioenteric anastomosis, followed by the rapid disappearance of LpX, paralleling the normalization of serum lipids, bilirubin, and bile acids, with a progressive reduction of hepatobiliary enzymes.ConclusionWe have described a unique case of focal non-neoplastic extrahepatic biliary stenosis of uncertain etiology, presenting with unusual extremely high levels of LpX-mediated hypercholesterolemia, a condition which is frequently mistaken for LDL on routine clinical tests.

Association of novel TMEM67 variants with mild phenotypes of high gamma-glutamyl transpeptidase cholestasis and congenital hepatic fibrosis.

TMEM67 (mecklin or MKS3) locates in the transition zone of cilia. Dysfunction of TMEM67 disrupts cilia-related signaling and leads to developmental defects of multiple organs in humans. Typical autosomal recessive TMEM67 defects cause partial overlapping phenotypes, including abnormalities in the brain, eyes, liver, kidneys, bones, and so forth. However, emerging reports of isolated nephronophthisis suggest the possibility of a broader phenotype spectrum. In this study, we analyzed the genetic data of cholestasis patients with no obvious extrahepatic involvement but with an unexplained high level of gamma-glutamyl transpeptidase (GGT). We identified five Han Chinese patients from three unrelated families with biallelic nonnull low-frequency TMEM67 variants. All variants were predicted pathogenic in silico, of which p. Arg820Ile and p. Leu144del were previously unreported. In vitro studies revealed that the protein levels of the TMEM67 variants were significantly decreased; however, their interaction with MKS1 remained unaffected. All the patients, aged 7-39 years old, had silently progressive cholestasis with elevated GGT but had normal bilirubin levels. Histological studies of liver biopsy of patients 1, 3, and 5 showed the presence of congenital hepatic fibrosis. We conclude that variants in TMEM67 are associated with a mild phenotype of unexplained, persistent, anicteric, and high GGT cholestasis without typical symptoms of TMEM67 defects; this possibility should be considered by physicians in gastroenterology and hepatology.

Multidisciplinary Management of Alagille Syndrome.

Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart, kidneys, eyes and major blood vessels. With myriads of presentations across different age groups, ALGS is usually suspected in infants presenting with high gamma glutamyl transpeptidase cholestasis and/or congenital heart disease. In children it may present with decompensated cirrhosis, intellectual disability or short stature, and in adults vascular events like stroke or ruptured berry aneurysm are more commonly noted. Liver transplantation (LT) is indicated in children with cholestasis progressing to cirrhosis with decompensation. Other indications for LT include intractable pruritus, recurrent fractures, hepatocellular carcinoma and disfiguring xanthomas. Due to an increased risk of renal impairment noted in ALGS, these patients would require optimized renal sparing immunosuppression in the post-transplant period. As the systemic manifestations of ALGS are protean and a wider spectrum is being increasingly elucidated, a multidisciplinary team needs to be involved in managing these patients. Moreover, many basic-science and clinical questions especially with regard to its presentation and management remain unanswered. The aim of this review is to provide updated insights into the management of the multi-system involvement of ALGS.

The Liver Biopsy in Neonatal Cholestasis: Just a Cherry on Top?

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Association Between Gamma-Glutamyl Transferase, Total Bilirubin and Systemic Lupus Erythematosus in Chinese Women.

BackgroundSystemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored.MethodWe recruited 341 SLE patients and 332 healthy individuals in Liaocheng People’s Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE.ResultsWe found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (rs=0.417) and IL-6 (rs=0.412), inversely proportional to C3 (rs=-0.177) and C4 (rs=0.-132). TBIL was inversely proportional to CRP (rs=-0.328) and TNF(rs=-0.360), and positively proportional to C3 (rs=0.174) and C4 (rs=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42–6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27–5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51–9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUCCOMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUCGGT=0.612, AUCTBIL=0.614).ConclusionWe found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.

A ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant

BackgroundZFYVE19 (Zinc Finger FYVE-Type Containing 19) mutations have most recently been associated to a novel type of high gamma-glutamyl transpeptidase (GGT), non-syndromic, neonatal-onset intrahepatic chronic cholestasis possibly associated to cilia dysfunction. Herein, we report a new case with further studies of whole exome sequencing (WES) and immunofluorescence in primary cilia of her cultured fibroblasts which confirm the observation.ResultsA now 5-year-old girl born to clinically healthy consanguineous Moroccan parents was assessed at 59 days of life due to severe cholestatic jaundice with increased serum bile acids and GGT, and preserved hepatocellular synthetic function. Despite fibrosis/cirrhosis and biliary ducts proliferation on liver biopsy suggested an extrahepatic biliary obstacle, normal intra-operatory cholangiography excluded biliary atresia. Under choleretic treatment, she maintained a clinically stable anicteric cholestasis but developped hyperlipidemia. After exclusion of the main causes of cholestasis by multiple tests, abnormal concentrations of sterols and WES led to a diagnosis of hereditary sitosterolemia (OMIM #618666), likely unrelated to her cholestasis. Further sequencing investigation revealed a homozygous non-sense mutation (p.Arg223Ter) in ZFYVE19 leading to a 222 aa truncated protein and present in both heterozygous parents. Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed a ciliary phenotype mainly defined by fragmented cilia and centrioles abnormalities.ConclusionsOur findings are consistent with and expands the recent evidence linking ZFYVE19 to a novel, likely non-syndromic, high GGT-PFIC phenotype with neonatal onset. Due to the possible role of ZFYVE19 in cilia function and the unprecedented coexistence of a coincidental hereditary sterol disorder in our case, continuous monitoring will be necessary to substantiate type of liver disease progression and/or possible emergence of a multisystemic involvement. What mentioned above confirms that the application of WES in children with undiagnosed cholestasis may lead to the identification of new causative genes, widening the knowledge on the pathophysiology.

High serum gamma-glutamyl transpeptidase concentration associates with poor postoperative prognosis of patients with hepatitis B virus-associated intrahepatic cholangiocarcinoma.

BackgroundIntrahepatic cholangiocarcinoma (ICC) caused by chronic hepatitis B virus (HBV) infection has become prominent. Prospectively stratifying postoperative risk factors is a challenging task.MethodsWe retrospectively assessed the relationship between serum gamma-glutamyl transpeptidase (GGT) concentration and postoperative outcomes in 107 subjects with HBV-associated ICC. Cox proportionate hazard models and subgroup analyses were used to test the hypothesis with adjustment for potential confounders.ResultsSerum GGT concentration was negatively correlated with postoperative outcomes. For a 1-standard deviation (per-SD) (117 µ/L) increase of serum GGT concentration, the relative risk (RR) for overall survival (OS) and time to recurrence (TTR) were 1.72 [95% confidence interval (CI), 1.37 to 2.16] and 1.53 (95% CI, 1.22 to 1.91), respectively. In addition, the RRs of middle and top tertiles of GGT for death were 1.81 (95% CI, 0.98 to 3.32) and 3.56 (95% CI, 1.97 to 6.42), respectively (P for trend <0.001). Similarly, the RRs for recurrence of the corresponding tertiles were 1.70 (95% CI, 0.93 to 3.10) and 3.27 (95% CI, 1.77 to 6.06), respectively (P for trend =0.002). In our study, the negative correlation between serum GGT levels and OS did not differ significantly between groups stratified by age, sex, HBV DNA level, carbohydrate antigen 19-9 (CA19-9) level and liver resection type (all P for interaction >0.05); however, there was a significant interactive effect of serum GGT and adjuvant chemotherapy on OS (RR =0.64 vs. 1.77, P for interaction =0.04).ConclusionsHigh serum GGT concentration is associated with an increased risk of postoperative death and tumor recurrence in patients with HBV-associated ICC. However, this relationship became less significant with the implementation of adjuvant chemotherapy.

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations.

The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0–8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14–1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19.

Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.

Red Blood Cell Distribution Width-to-Platelet Ratio and Other Laboratory Indices Associated with Severity of Histological Hepatic Fibrosis in Patients with Autoimmune Hepatitis: A Retrospective Study at a Single Center.

BackgroundThis retrospective study at a single center aimed to evaluate the role of the red blood cell distribution width (RDW)-to-platelet ratio and other laboratory indices associated with the severity of histological hepatic fibrosis on liver biopsy in patients with autoimmune hepatitis (AIH).Material/MethodsWe retrospectively reviewed records from 2097 adult patients who had liver biopsies. Of these patients, data from 72 with AIH and 164 with drug-induced liver injury (DILI) with complete laboratory information and medical histories were included in the analysis.ResultsWe found that compared with patients with DILI, patients with AIH had higher alkaline phosphatase, globulin, and total bile acid levels. Multivariate analyses of risk factors for AIH-associated advanced liver fibrosis in Chinese patients revealed an estimated adjusted odds ratio (AOR) (95% CI) of 1.609 (1.028–2.517) in patients with higher immunoglobulin A (IgA) levels. Patients with higher gamma-glutamyl transpeptidase (GGT)-to-platelet ratio (GPR) values had a significantly higher risk of serious liver fibrosis than patients with lower GPR values. Advanced fibrosis risk was higher in patients with higher RPR values than in patients with lower RPR values [AOR (95% CI): 25.507 (2.934–221.784)]. The result for area under the curve (0.821) analysis for lnRPR levels indicated this variable had high diagnostic performance for predicting advanced AIH-related fibrosis.ConclusionsThe degree of histological liver fibrosis in patients with AIH was significantly associated with an increased red blood cell distribution width-to-platelet ratio, GPR, and increased serum levels of IgA.

Insulin resistance and hepatic steatosis in type 1 diabetes mellitus and their association with diabetic chronic complications.

To evaluate insulin resistance and hepatic steatosis and their association with diabetes duration, control and chronic complications in patients with type 1 diabetes. We studied medical records of 181 consecutive hospitalized adults patients with type 1 diabetes. Estimated glucose disposal rate (eGDR), insulin sensitivity score (ISS), fatty liver index (FLI) and hepatic steatosis index (HSI) were calculated. Patients in the 1st tertile of eGDR (<4.1 mg/kg-1-min-1) and ISS (<4.8) had higher prevalence of ischemic cardiovascular disease (ICVD) (p<0.001), hepatic steatosis, higher gamma glutamyl transpeptidase, HSI, FLI compared with participants from the 2nd and 3rd tertile of eGDR and ISS. Compared with those without steatosis, patients with ultrasound-diagnosed steatosis (30.5%) had a higher ISS (4.4±1.9 vs 6.3±2.4, p<0.001), eGDR (4.5±3.0 vs 5.8±2.7, p=0.01), FLI (72.5±25.1 vs 51.0±27.2, p<0.001), HSI (37.5±6.1 vs 35.2±4.7, p=0.03) and prevalence of ICVD (71.7 vs 45.7%, p=0.004) and retinopathy (69.6 vs 52.4 %, p=0.03). Factors independently associated with hepatic steatosis were only ICVD (OR 0.148, p<0.001), ISS (OR=2.584, p=0.029), aspartate aminotransferase (OR=1.025, p=0.038) and male gender (OR=2.726, p=0.016). Insulin resistance and hepatic steatosis are common in type 1 diabetes and have a significant association with ICVD, independently of diabetes duration, control and insulin doses.

Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma.

ObjectiveTo investigate the risk factors of early postoperative recurrence in patients with single and small (≤3 cm) hepatitis B virus-associated primary hepatocellular carcinoma (HBV-HCC).MethodsThis retrospective study analyzed patients with single and small HBV-HCC. All patients were followed up for 1 year after surgery.ResultsAmong 182 patients, 54 patients had early recurrence within 1 year. The recurrence group had higher proportions of men, drinking history, Child–Turcotte–Pugh (CTP) class C, patients who underwent transarterial chemoembolization (TACE), and serum alpha-fetoprotein (AFP) >10 ng/mL as well as higher gamma-glutamyl transpeptidase (GGT) levels and lower total protein (TP) and CD8+ T lymphocyte levels than the no recurrence group. Cox multivariate regression analysis demonstrated that drinking history (HR, 1.312; 95% CI, 1.042–1.652), CTP class C (HR, 1.236; 95% CI, 1.037–1.473), TACE treatment (HR, 1.241; 95% CI, 1.026–1.501), GGT (HR, 1.138; 95% CI, 1.042–1.243), TP (HR, 0.729; 95% CI, 0.555–0.957), and AFP (HR, 2.519; 95% CI, 1.343–4.726) were independently associated with early postoperative recurrence.ConclusionDrinking history, CTP class C, TACE, serum AFP, GGT, and TP levels were independently associated with early postoperative recurrence in patients with single and small HBV-HCC.

Serum Gamma Glutamyl transferase is a predictor of recurrence after R0 hepatectomy for patients with colorectal cancer liver metastases.

Objectives:Gamma glutamyl-transpeptidase (GGT) has been shown as a prognostic marker in many cancers. The aim of this study was to explore whether serum GGT could predict tumor recurrence in patients with liver-confined colorectal cancer liver metastases (CRCLM) undergoing R0 resection.Methods:We reviewed patients who had underwent liver surgery for CRCLM. Patients with liver-only metastases that underwent R0 resection were included. Pre-operative serum GGT were classified into either high or low using a cut-off value of 33 U/L for female and 51 U/L for male. Relapse-free survival (RFS) was compared in relation to GGT and other clinicopathological factors.Results:Of the 350 patients included, 108 (30.9%) had a high serum GGT. Patients with metachronous liver metastases, number of metastases ⩾2, size of the largest metastasis ⩾3 cm, or a history of neoadjuvant chemotherapy had a higher GGT level (p = 0.001, 0.027, 0.001, and 0.002, respectively). In survival analyses, patients with a high GGT had a shorter RFS than those with a low GGT, with a median RFS of 11.8 versus 30.3 months (p < 0.001). RFS was also associated with the number of metastases, size of the largest metastasis and the delivery of neoadjuvant chemotherapy. In multivariate analysis, GGT remained an independent prognostic factor of RFS.Conclusions:Our study demonstrates that the serum GGT level before liver surgery is an adverse prognostic factor of RFS for patients with liver-confined CRCLM.

High hairy and enhancer of split 1 and low SOX17 immunohistochemical hepatic expression is associated with human biliary atresia

Background Early discrimination of biliary atresia (BA) from other causes of neonatal cholestasis is a cornerstone for successful surgical intervention. To date, the exact etiology of BA remains elusive. We aimed to investigate the hepatic expression of hairy and enhancer of split 1 (HES1) and SOX17 in infants with BA compared with non-BA causes of cholestasis. Methods The study included 61 infants with cholestasis in two groups, BA (n=32) and non-BA (n=29). HES1 and SOX17 hepatic expression was evaluated in biliary epithelial cells as proportion×intensity for the total score. Results The frequency of positive HES1 expression was significantly higher in BA (84.8%) compared with non-BA (35.7%). In addition, the HES1 score was significantly higher in BA than in non-BA. The frequency of high intensity staining was significantly higher in BA (50%) compared with non-BA (20%). All patients were positive for SOX17. The SOX17 score was significantly lower in BA compared with non-BA. Furthermore, the occurrence of low-intensity staining was significantly higher in BA (84.4%) compared with non-BA (46.4%). Clay stool, higher gamma glutamyl transpeptidase, ductular proliferation, bile plugs, and portal edema are associated with positive HES1 and low SOX17 expression. Furthermore, abnormal gallbladder is associated with low SOX17 expression. Conclusion Positive HES1 and low SOX17 expression are associated significantly with BA. These results support the potential role of these molecules in the etiopathogenesis of BA.

Risk factors associated with nonalcohol fatty liver disease and fibrosis among patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is closely related to hepatic steatosis and fibrosis. The aim of this study was to analyze the occurrence of hepatic steatosis and fibrosis in patients with T2DM and to explore the risk factors.A total of 629 patients with T2DM were enrolled. Liver stiffness value (LSV) and controlled attenuation parameters (CAP) were measured using Fibroscan. Liver fibrosis was diagnosed when LSV was greater than 7.4 kPa, and advanced liver fibrosis was diagnosed when LSV was greater than 10.6 kPa. Hepatic steatosis diagnosis was made when CAP value was greater than 238 dB/m. Demographic information, physical examination data, and laboratory tests results were collected. The 629 patients were classified into 2 groups by the liver fibrosis and liver steatosis, and then the difference was analyzed.Among patients enrolled, 231 patients were diagnosed as liver fibrosis. The age of the patients in the fibrosis group was significantly greater than that in the non-fibrosis group, and similar trends were observed in the waist–hip ratio (WHR), systolic blood pressure, and diastolic blood pressure. The proportion of smoking and alcoholic consumption was significantly lower in patients with non-fibrosis group. A total of 426 patients were diagnosed with liver steatosis. Body mass index (BMI), WHR, systolic blood pressure, and diastolic blood pressure in patients with steatosis were significantly higher than those in non-steatosis group. We observed that the LSV (P = .042) and CAP value (P < .001) are positively correlated with metabolic syndrome components in T2DM patients. Older age (OR = 1.099, P = .001), high BMI (OR = 1.088, P = .003), low platelet level (OR = 0.996, P = .014), and smoking (OR = 1.653, P = .013) were independent risk factors of liver fibrosis among T2DM patients. High BMI (OR = 1.369, P < .001), high diastolic blood pressure (OR = 1.048, P < .001), and high gamma glutamyl transpeptidase (OR = 1.018, P = .009) were independent risk factors for liver steatosis among T2DM patients.This study suggested risk factors screening of liver fibrosis and steatosis. Timely intervention should be taken into consideration among high risk patients to prevent progress liver diseases.

Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.

HIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated. We stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined. AST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03). We identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS.

Limited Diagnostic Significance of Gamma Glutamyl Transpeptidase Levels in Advanced Pediatric Cholestatic Liver Diseases

Serum Gamma Glutamyl Transpeptidase (GGTP), a useful screening test for diagnosis of pediatric cholestatic liver disorders, may show a progressive fall in patients with high GGTP cholestasis at baseline with failing hepatic functions, leading to erroneous interpretation. So, this study was aimed to check the diagnostic significance of GGTP values in advanced high GGTP pediatric cholestatic liver diseases. Seven prototype cases (4 cases of biliary atresia, 2 cases of progressive familial intrahepatic cholestasis type 3 and 1 case of primary sclerosing cholangitis(with complete workup and adequate follow up) were evaluated in detail. In these cases, serum GGTP levels initially remained high and gradually went down as the disease progressed i.e decompensation of hepatic function occurred. The study thus concluded that serum GGTP levels should not be used in isolation to consider a differential diagnosis of pediatric cholestatic disorders in resource constraint countries and should always be used in conjunction with hepatic synthetic functions and clinical picture to avoid misinterpretation.