Elevated Serum Gamma-glutamyl Transpeptidase Research Articles

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.

Predictive Factors for Two-Year Survival in Dogs with Hepatobiliary Diseases: Importance of Clinical and Laboratory Monitoring.

Long-term outcomes and survival predictors for different clinicopathologies (idiopathic chronic hepatitis, liver fibrosis, vacuolar hepatopathy) in dogs with hepatobiliary diseases are poorly described. In this study, ninety dogs were followed up for up to five years to investigate clinical factors that predict two-year survival in canine patients after liver biopsy. Univariate and multivariate analyses were performed based on clinical and laboratory data to determine the association between clinical and laboratory data and mortality rates. Overall, the one-, two-, and five-year mortality rates were 28.9%, 45.6%, and 78.9%, respectively. Univariate analysis indicated that male gender, ascites, elevated serum gamma-glutamyl transpeptidase (GGT), hypercholesterolemia, hypoalbuminemia, prolonged activated partial thromboplastin clotting time (aPTT), and prolonged thrombin clotting time (TT) were associated with an increased two-year mortality rate. Results from multivariate analysis demonstrated a significant association between male gender (p = 0.022), elevated serum GGT (p < 0.001), hypoalbuminemia (p < 0.001), and prolonged aPTT (p < 0.001) and an increased two-year mortality rate, regardless of the specific type of liver pathology. Elevated GGT was associated with the highest risk for increased two-year mortality (95% CI: hazard ratio 6.02-41.21). In conclusion, various clinical factors in dogs with liver diseases are useful for prognosis prediction.

Development and Validation of a Prognostic Nomogram to Predict the Long-Time Prognosis in Non-B, Non-C Hepatocellular Carcinoma.

PurposeTo develop and validate a nomogram for individualized prediction of the long-term prognosis of patients with non-B, non-C hepatocellular carcinoma (NBNC-HCC) who underwent hepatectomy.Materials and MethodsFive hundred ninety-four patients who met the criteria were included in the research and randomly categorized into the training or validation cohort. The nomogram was constructed on the basis of the independent risk variables that were acquired via multivariate Cox proportional hazard regression analysis. Several complementary methods included the Harrell c-index, time-dependent areas under the receiver operating characteristic curve (tdAUC), and calibration plot, and the Kaplan–Meier curve with Log rank test were used to test predictive performance of the model. The clinical utility of the model was tested by the decision cure analysis (DCA).ResultsTumor diameter, tumor number, elevated serum gamma-glutamyl transpeptidase (GGT) level, microvascular invasion (MVI), and macrovascular invasion were independent risk factors of prognosis of NBNC-HCC. C-indexes of the nomogram were 0.702 (95% confidence interval [CI], 0.662–0.741) in the training cohort and 0.700 (95% CI, 0.643–0.758) in the validation cohort, and median tdAUC values of the nomogram were 0.743 (range, 0.736–0.775) in the training cohort and 0.751 (range, 0.686–0.793) in the validation cohort, which were both higher than those in the conventionally used Barcelona Clinic Liver Cancer staging system, American Joint Committee on Cancer, and eighth edition and the model of Zhang et al. The calibration plot depicted a good consistency between prediction of the model and observed outcome. The Kaplan–Meier curve analysis showed that the model was able to separate patients into three distinct risk subgroups. The DCA analysis also demonstrated that the nomogram was clinically useful.ConclusionWe developed and validated a nomogram that was accurate and clinically useful in patients with NBNC-HCC who underwent hepatectomy.

Gamma glutamyl transpeptidase as a prognostic biomarker in hepatocellular cancer patients especially with >5 cm tumors, treated by liver transplantation.

Serum AFP levels are typically elevated in less than 50% of hepatocellular cancer (HCC) patients. Gamma-glutamyl transpeptidase (GGT) levels have been suggested to be a potentially useful HCC biomarker. To assess in a cohort of prospectively evaluated HCC patients who underwent liver transplant and whose survival was known; the occurrence, prognosis, and clinical characteristics of patients with elevated serum GGT levels. Serum GGT levels were found to be elevated in a higher proportion in patients with either small or large HCC than alpha-fetoprotein (AFP) levels, and were significantly related to prognosis in patients with large size HCCs. There was no clear correlation between GGT and AFP levels, likely reflecting different HCC characteristics or HCC cell lineages associated with these two markers. Furthermore, elevated GGT was found in 24% of low-AFP patients with small tumors and 46% with large tumors. Elevated GGT levels were also significantly associated with microvascular invasion and tumor diameter. Elevated serum GGT levels were associated with HCC size and worse survival, and were unrelated to AFP levels. GGT may be a useful prognostic tumor marker, especially for low-AFP HCC patients.

Management for elevated serum Gamma Glutamyl Transpeptidase in primary care settings

Management for elevated serum Gamma Glutamyl Transpeptidase in primary care settings

Erratum to: Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n=36) or a placebo group (n=39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. Significant group×time interactions for serum levels of GGT (F=3.98, P=0.022) and alanine aminotransferase (ALT; F=3.28, P=0.043) were observed with an improvement in levels of GGT (P=0.066) and ALT (P=0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

Elevated Preoperative Serum Gamma-glutamyltranspeptidase Predicts Poor Prognosis for Hepatocellular Carcinoma after Liver Transplantation.

Gamma-glutamyltransferase (γ-GGT) is a membrane-bound enzyme that is involved in biotransformation, nucleic acid metabolism, and tumourigenesis. Elevated serum γ-GGT levels are related to an increased cancer risk and worse prognosis in many cancers. In the present study, we evaluated the prognostic value of preoperative serum γ-GGT in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). A total of 130 HCC patients after LT were included in the study. The optimal cut-off value of γ-GGT was 128U/L by receiver operating characteristic analysis, with a sensitivity and specificity of 60.0% and 72.9%, respectively. Elevated preoperative serum γ-GGT was significantly associated with high alpha-fetoprotein (AFP), large tumor size, and macro- and micro-vascular invasion. The 1-, 3-, 5-year disease-free survival (DFS) and overall survival (OS) rates of HCC patients in the γ-GGT > 128U/L group were poorer than those in the γ-GGT ≤ 128U/L group. Stratification analysis revealed that γ-GGT exhibited a greater predictive value for DFS and OS in HCC patients beyond the Milan criteria and no macro-vascular invasion. In conclusion, elevated preoperative serum γ-GGT was significantly associated with advanced tumor stage and aggressive tumor behaviors, and serum γ-GGT can be considered as a prognostic factor for HCC patients after LT, especially for patients beyond the Milan criteria or without macro-vascular invasion.

Outcomes of Hepatic Resection in Intrahepatic Cholangiocarcinoma Patients with Diabetes, Hypertension, and Dyslipidemia: Significance of Routine Follow-Up

Background: The outcomes of hepatic resection in intrahepatic cholangiocarcinoma (ICC) patients with diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DL) (metabolic components) remain unclear. Methods: The outcomes of 43 ICC patients without known risk factors for ICC who underwent hepatic resection were retrospectively reviewed. These patients were divided into three groups: those followed-up for metabolic components at least every 6 months (follow-up group, n=16), those not followed-up for metabolic components (no follow-up group, n=14), and those without metabolic components (control group, n=13). Results: In the follow-up group, 13 (81%) patients were further examined for ICC during follow-up because of abnormal screening results, such as elevated serum gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 (CA19-9) concentrations or detection of hepatic tumor on ultrasonography and/or computed tomography, whereas most patients in the other two groups exhibited ICC-related symptoms. No patient in the follow-up group exhibited lymph node metastasis, whereas 43% of those in the no follow-up group and 46% in the control group had lymph node metastasis (p=0.005 and 0.004 vs. the follow-up group, respectively). All 16 patients in the follow-up group were diagnosed as International Union Against Cancer pathologic stage I or II (early stage). There were no significant differences in the incidence of postoperative recurrence between the three groups; however, the incidence of extrahepatic recurrence was lower in the follow-up group than in the no follow-up group and the control group (13% vs. 78% vs. 63%, p=0.0232). The 1-, 3-, and 5-year overall survivalrates in the follow-up group were better than those in the no follow-up and control groups (93/93/66% vs. 77/34/34% and 85/24/0%, p=0.034 and 0.001, respectively). Conclusions: Routine measurement of serum gamma-glutamyl transpeptidase and/or CA19-9 levels and imaging examinations every 12 months (or 6 months, if possible) are recommended during follow-up for DM, HT, and DL to detect ICC at an early stage.

Treatment of chronic HCV Genotype 1 infection with Boceprevir in German real-life:The impact of SVR on initially elevated and initially normal serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels

Background: Patients (pts) with chronic HCV G1 infection may present with normal or elevated serum ALT or GGT levels. The aim of the present analysis was to investigate the effect of successful treatment of chronic HCV G1 infection with boceprevir (BOC) triple therapy on initially elevated and initially normal ALT and GGT levels.

Elevated Serum Gamma-glutamyl Transpeptidase Levels and Fatty Liver Strongly Predict the Presence of Carotid Plaque.

There is a strong relationship between carotid atherosclerosis and future cardiovascular disease (CVD). This study sought to clarify the association of fatty liver and an elevated serum gamma-glutamyl transpeptidase (GGT) level with carotid atherosclerosis. We reviewed the medical records of subjects who underwent medical checkups at our institute. Carotid atherosclerosis and fatty liver were assessed using ultrasound (US), and predictors of increased carotid intima-media thickness (IMT) and carotid plaque were identified using a logistic regression model. In total, 958 subjects (564 men, 394 women; median age, 59 years) were enrolled. The median value of the mean carotid IMT was 0.713 mm, and the frequency of carotid plaque was 19.5%. For the highest quartile of the mean carotid IMT (≥ 0.863 mm), a male sex, older age, hypertension (HT), dyslipidemia (DL) and type 2 diabetes mellitus (DM) were identified as independent predictors. A male sex, older age, HT and elevated serum GGT level were found to be significant predictors of the presence of carotid plaque. In addition, fatty liver correlated with the existence of carotid plaque. When the combination of the serum GGT level and presence or absence of fatty liver was included as a variable in the analysis, a male sex, older age, HT and fatty liver with a serum GGT level of ≥ 83 IU/L (90th percentile) (odds ratio 3.21, 95% confidence interval 1.27-8.12, p=0.014)were identified to be significantly associated with carotid plaque. This study suggests that the simultaneous presence of an elevated serum GGT level and fatty liver is highly predictive of carotid plaque.

Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

Background: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes. Aims: To study if and how GGT is correlated with mortality following liver transplantation. Methods: We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Results: Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p<0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not ( p<0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival ( p<0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival ( p<0.001). Conclusions: These paradoxical findings may be explained by the time-dependent role of GGT in glutathione metabolism. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response.

Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival.

Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes. To study if and how GGT is correlated with mortality following liver transplantation. We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p<0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not ( p<0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival ( p<0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival ( p<0.001). These paradoxical findings may be explained by the time-dependent role of GGT in glutathione metabolism. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response.

Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

Background: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes. Aims : To study if and how GGT is correlated with mortality following liver transplantation. Methods: We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Results: Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p &lt;0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not ( p &lt;0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival ( p &lt;0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival ( p &lt;0.001). Conclusions:&nbsp; These paradoxical findings may be explained by the time-dependent role of GGT in glutathione metabolism. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response.

Non‐alcoholic fatty liver disease in diabetics – prevalence and predictive factors in a multiracial hospital clinic population in Malaysia

There is currently no published study comparing prevalence of non-alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia-Pacific region. Cross-sectional study of consecutive patients in the Diabetic Clinic in University of Malaya Medical Centre. The Global Physical Activity Questionnaire and a semiquantitative food-frequency questionnaire were used to assess physical activity and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake. Data for 399 patients were analyzed (mean age 62.3 ± 10.5 years, 43.1% men). The racial distribution was Chinese 43.6%, Indian 33.1%, Malay 22.3%, and others 1.0%. The prevalence of NAFLD was 49.6%. On univariate analysis, factors associated with NAFLD were age < 65 years, race, obesity, central obesity, glycated hemoglobin ≥ 7.0%, and elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels. Patients with low physical activity were more likely to have NAFLD (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.06-2.63, P = 0.020). The prevalence of NAFLD was highest among Malays (60.7%), followed by Indians (51.5%), and lowest among Chinese (42.0%) consistent with higher prevalence of central obesity and higher percentage calorie intake from fat in the former groups of patients. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR = 2.20, 95% CI = 1.29-3.75, P = 0.004) and elevated serum ALT level (OR = 1.98, 95% CI = 1.21-3.25, P = 0.007). NAFLD was seen in half of a cohort of diabetic patients and was independently associated with central obesity and elevated serum ALT level. Prevalence of NAFLD was different and paralleled the difference in prevalence of central obesity and in percentage calorie intake from fat among the different ethnic groups.

Serum gammaglutamyl transpeptidase, alkaline phosphatase, and alfa-fetoprotein in small HCCs.

e14528 Background: We previously analyzed a large cohort of unresectable HCC patients, ordered by survival. Significant new prognostic factors included gamma glutamyltranspeptidase (GGTP) and alkaline phosphatase (ALKP), as well as previously-described alfa-fetoprotein (AFP). We wished to extend this approach to analysis of small tumors, which could have significance for screening, given AFP limitations. Methods: A further 557 patients with small HCCs who were diagnosed by screening, were analyzed for baseline serum GGTP, ALKP and AFP and ordered by tumor mass (size x number) and tumor number (one or > one). Results: 355 patients (pts) had tumor mass <3 (small) and 202 pts had mass >3 (larger). Small vs. larger tumors with GGTP >45 IU/l were 42% vs. 64%, AFP >25 ng/ml were 32% vs. 43%, ALKP >120 IU/l were 19% vs. 30%. Liver function was excellent, with total bilirubin being <1.3 mg/dl in 88% of each group and albumin being >3g/dl 96% of small and 95% of larger tumors. Thus, GGTP was elevated in 50% more pts than AFP in each group. The cohort was then analyzed according to presence of a single (73% of total) or more than one tumor. For 1 vs. >1 tumor, results were: elevated GGTP 46% vs. 59%, elevated AFP 37% vs. 41%, elevated ALKP 16% vs. 22%. Total bilirubin and albumin levels were similarly normal. For tumor mass <3, 100% of pts had a single tumor; for tumor mass >3, 25% pts had a single tumor and 75% had >1. Age was remarkable as at <65 yrs (61% of pts) all pts had only a single tumor with <3 tumor mass at <3cm diameter. For pts >65 yr (39% of pts) there was a steady increase in tumor size and # with age. Conclusions: For pts with small tumors and normal bilirubin who were diagnosed by radiological screening, there was a much higher % with elevated serum GGTP than AFP.

Is Serum Gamma-Glutamyltransferase a Biomarker of Xenobiotics, Which Are Conjugated by Glutathione?

A meta-analysis of 10 prospective cohort studies,1 including our own,2 reported that serum γ-glutamyltransferase (GGT) predicted incident vascular events. This meta-analysis posed one important, but unsolved question: why does serum GGT predict incident vascular events? In addition to vascular events, serum GGT predicts various important clinical outcomes including type 2 diabetes, metabolic syndrome, and renal problems.3–5 Serum GGT has traditionally been used as a marker of alcohol consumption; however, alcohol consumption cannot explain the disease relationships with serum GGT because these associations have been observed among nondrinkers as well as drinkers. The other prevailing interpretations are that serum GGT predicts clinical outcomes as a marker of nonalcoholic fatty liver disease (NAFLD) or oxidative stress.6–8 Although both of these explanations have some merit, each also has problems. Although not clearly stated in many of the reports,1–5 most associations of serum GGT with clinical outcomes were dose-response relations within the normal range of serum GGT; we submit that this aspect of the association is critical to interpretation. First, even though NAFLD may partially explain the associations among subjects with a relatively high serum GGT activity and NAFLD can present even among subjects with low normal serum GGT, NAFLD is unlikely to fully explain the graded associations with clinical outcomes which were observed among subjects with serum GGT in the low part of its normal range, less than 20 or 30 U/L. However, it is worthwhile to note that serum GGT may be a predictor of the future risk of NAFLD. In a prospective study by our group,9 serum GGT within its normal range strongly predicted the future risk of chronic elevation of serum alanine aminotransferase (ALT), but serum ALT within its normal range did not predict the future risk of chronic elevation of serum GGT. The …

Hepatitic inherited metabolic disorders

Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end-stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC-2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes.

Erythromycin-Associated Cholestatic Hepatitis and Liver Dysfunction in Children: The British Experience

Journal of Clinical Gastroenterology: September 2005 - Volume 39 - Issue 8 - p 743-744 doi: 10.1097/01.mcg.0000173931.67739.41