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| 1 | Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics显示文摘Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury. | Pierluigi Marzuillo Anna Grandone Laura Perrone Emanuele Miraglia del Giudice | 2015 | World Journal of Hepatology2015，7，11： | 9 |
| 2 | TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype显示文摘AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected patients.METHODS The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was observed.CONCLUSION In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype. | Caterina Sagnelli Marco Merli Caterina Uberti-Foppa Hamid Hasson Anna Grandone Grazia Cirillo Stefania Salpietro Carmine Minichini Mario Starace Emanuela Messina Patrizia Morelli Emanuele Miraglia Del Giudice Adriano Lazzarin Nicola Coppola Evangelista Sagnelli | 2016 | World Journal of Gastroenterology2016，22，38： | 4 |
| 3 | TM 6 SF 2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA 3 polymorphism显示文摘 | Nicola Coppola Zampino Rosa Grazia Cirillo Maria Stanzione Margherita Macera Adriana Boemio Anna Grandone Mariantonietta Pisaturo Aldo Marrone Luigi E. Adinolfi Evangelista Sagnelli Emanuele Miraglia del Giudice | 2015 | Liver Int2015，，8： | 3 |
| 4 | Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis显示文摘 | Lucio Amitrano Maria Anna Guardascione Vincenzo Brancaccio Maurizio Margaglione Francesco Manguso Luigi Iannaccone Elvira Grandone Antonio Balzano | 2004 | Journal of Hepatology2004，，5： | 2 |
| 5 | Homocysteine levels in amniotic fluid显示文摘 | Grandone E Colaizzo D Vecehione G | 2006 | Relationship with birth-weight Thromb Haemost2006，95，4： | 1 |
| 6 | Determining sulfor-containing amino acids by capillary electrophoresis: a fast novel method for total homocysteine human plasma 显示文摘 | Margaglione M Grandone E | 1999 | Electrophoresis1999，20，3： | 1 |
| 7 | Electronic commerce adoption: an empirical study of small and medium US businesses 显示文摘 | Grandon E E Pearson J M | 2004 | Information & Management2004，42，1： | 1 |
| 8 | Plasminogen activator inhibitor-1 (PAI-1) antigen plasma levels in subjects attending a metabolic ward:relation to polymorphisms of PAI-1 and angiontensin converting enzyme (ACE) genes显示文摘 | Margaglione M Grandone E Vecchione G | 1997 | Arterioscler Thromb Vasc Biol1997，17，10： | 1 |
| 9 | Electrocoagulation as a Remediation Tool for Wastewaterscontaining Arsenicv显示文摘 | Henrik K Hansen Patricio Nuez Rodrigo Grandon | 2006 | Minerals Engineering2006，19，： | 1 |
| 10 | Determining sulfor-containing amino by capillary electrophoresis:a fast novel mothod for total homocysteine human plasma显示文摘 | Vecchione G Margaglione M Grandone E | 1999 | Electrophoresis1999，20，3： | 1 |
| 11 | Genetic Modulation of Plasma Fibrinogen Concentrations:Possible Importance of Interleukin-6显示文摘 | Margaglione M Grandone E Mancini FP el al | 1996 | J Thromb Thrombolysis1996，3，1： | 1 |
| 12 | Clinical evaluation of hexagonal keratotomy for the treatment of primary hyperopia 显示文摘 | Grandon SC Sanders DR Anello RD | 1995 | J Cataract Refract Surg1995，21，： | 1 |
| 13 | Novel cAMP binding protein-BP (CREBBP) mutation in a girl with Rubinstein-Taybi syndrome,GH deficiency,Arnold Chiari malformation and pituitary hypoplasia显示文摘 | Marzuillo P Grandone A Coppola R | 2013 | BMC Med Genet2013，14，： | 1 |
| 14 | Electronic commerce adoption: an empirical study of small and medium US businesses 显示文摘 | Grandon E E Pearson J M | 2004 | Information & management2004，42，1： | 1 |
| 15 | The C677T methyle- netetrahydrofolate reductase gene mutation does not influence cardiovas- cular risk in the dialysis population : results of a multicentre prospective study 显示文摘 | Aucella F Margaglione M Grandone E et at | 2005 | Nephrol Dial Transplant2005，20，2： | 1 |
| 16 | Subclinical myocardial dysfunction and cardiac autonomic dysregulation are closely associated in obese children and adolescents:the potential role of insulin resistance显示文摘 | Cozzolino D Grandone A Cittadini A | 2015 | PLo S One2015，10，01： | 1 |
| 17 | Electronic Commerce Adoption: An Empirical Study of Small and Medium US Businesses显示文摘 | Grandon E E Pear on J M | 2004 | Informa- tion & Management2004，42，1： | 1 |
| 18 | Genetic modulation of plasma fibrinogen concentrations:possible importance of interleukin -6显示文摘 | Margaglione M Grandone E Mancini FP | 1996 | J Thromb Thrombolysis1996，3，： | 1 |
| 19 | Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke 显示文摘 | Margaglion M Di Minno G Grandone E | 1994 | Arteriosclerosis1994，14，： | 1 |
| 20 | Genetic modulation of oral anticoagulation with warfarin显示文摘 | Margaglione M Colaizzo D D'Andrea G Brancaccio V Ciampa A Grandone E | 2000 | Thromb Haemost2000，84，： | 1 |
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