Serum concentrations of human insulin-like growth factor-1 and levels of insulin-like growth factor-binding protein-5 in patients with nonalcoholic fatty liver disease: association with liver histology.
ABSTRACT In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice.
Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay.
Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis.
Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.
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ABSTRACT: Child-Turcotte-Pugh (CTP) score is the standard tool to assess hepatic reserve in hepatocellular carcinoma (HCC), and CTP-A is the classic group for active therapy. However, CTP stratification accuracy has been questioned. We hypothesized that plasma insulin-like growth factor 1 (IGF-1) is a valid surrogate for hepatic reserve to replace the subjective parameters in CTP score to improve its prognostic accuracy. We retrospectively tested plasma IGF-1 levels in the training set (n = 310) from MD Anderson Cancer Center. Recursive partitioning identified three optimal IGF-1 ranges that correlated with overall survival (OS): greater than 50ng/mL = 1 point; 26 to 50ng/mL = 2 points; and less than 26ng/mL = 3 points. We modified the CTP score by replacing ascites and encephalopathy grading with plasma IGF-1 value (IGF-CTP) and subjected both scores to log-rank analysis. Harrell's C-index and U-statistics were used to compare the prognostic performance of both scores in both the training and validation cohorts (n = 155). All statistical tests were two-sided. Patients' stratification was statistically significantly stronger for IGF-CTP than CTP score for the training (P = .003) and the validation cohort (P = .005). Patients reclassified by IGF-CTP relative to their original CTP score were better stratified by their new risk groups. Most important, patients classified as A by CTP but B by IGF-CTP had statistically significantly worse OS than those who remained under class A by IGF-CTP in both cohorts (P = .03 and P < .001, respectively, from Cox regression models). AB patients had a worse OS than AA patients in both the training and validation set (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.03 to 2.04, P = .03; HR = 2.83, 95% CI = 1.65 to 4.85, P < .001, respectively). The IGF-CTP score is simple, blood-based, and cost-effective, stratified HCC better than CTP score, and validated well on two independent cohorts. International validation studies are warranted.CancerSpectrum Knowledge Environment 05/2014; · 14.07 Impact Factor
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ABSTRACT: Abstract Objective: The aim of this study was to investigate the association between metabolic syndrome and liver enzymes in overweight and obese adolescents and young adults. Methods: A total of 126 overweight and obese adolescents and young adults (age, 15-26 years), 55 (43.6%) with metabolic syndrome and 71 (56.4%) without metabolic syndrome, were studied. Results: Patients with metabolic syndrome had significantly higher alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) levels compared to patients without metabolic syndrome [36.5±22.2 vs. 29.4±17.8 IU/L (P=0.043), 33.8±17.8 vs. 26.9±18.4 IU/L (P=0.002), and 84.3±32.2 vs. 75.7±29.5 IU/L (P=0.063)]. Aspartate aminotransferase (AST) levels were similar in both groups (24.1±9.8 vs. 23.3±9.0 IU/L, P=0.674). Elevated AST, ALT, GGT, and ALP levels were observed in 6, 15, 18, and 5 patients (11%, 27%, 14%, and 9%) with metabolic syndrome compared to 6, 17, 6, and 4 (8%, 24%, 8% and 5%) patients without metabolic syndrome (P=0.872, P=0.826, P<0.001, and P=0.035). In multivariate regression models adjusted for age and gender, metabolic syndrome was not a significant predictor of ALT (P=0.967), GGT (P=0.526), and ALP levels (P=0.221), but insulin resistance was a significant predictor for ALT and GGT levels (P=0.001, P=0.028). Conclusion: Changes in liver function tests were observed in obese patients with metabolic syndrome, compared to patients without metabolic syndrome, especially in ALT and GGT levels. Insulin resistance is an independent pathogenic mechanism in liver function test changes regardless of metabolic syndrome in nondiabetic centrally obese youth.Metabolic syndrome and related disorders 08/2013;
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ABSTRACT: Objective To correlate circulating levels of insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein (IGFBP)-3 in a population of obese children with biopsy-proven nonalcoholic fatty liver disease (NAFLD) with clinical, biochemical, and histological features. Study design We conducted a cross-sectional study at the Hepatometabolic Unit of the Bambino Gesù Children's Hospital, Rome, Italy. Obese children (42 girls and 57 boys) underwent liver biopsy, anthropometry, biochemical assessment, and IGF system evaluation. Serum concentrations of IGF-I, IGF-II, and IGFBP-3 were measured. The liver biopsy features of each case were graded according to the NAFLD Activity Scoring system. The degrees of steatosis, inflammation, ballooning, and fibrosis were calculated. Results Nonalcoholic steatohepatitis was diagnosed in 14/99 obese subjects. Stepwise regression analysis revealed that IGF-I was the major predictor of ballooning (β = −0.463; P < .0001) and NAFLD activity score (β = −0.457; P < .0001), IGF-I/IGFBP-3 ratio was the major predictor of liver inflammation (β = -0.285; P = .005), and IGF-II was the major predictor of liver fibrosis (β = 0.343; P < .005). Conclusion Circulating levels of IGF-I and IGF-II are associated with the histological stages of NAFLD and may represent novel markers of liver damage progression in obese children.The Journal of pediatrics 01/2014; · 4.02 Impact Factor