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phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第14期22卷 3735-3745页

作者： Andrea Sanchez-Pareja Sophie Clément Marion Peyrou Laurent Spahr Francesco Negro laura rubbia-brandt Michelangelo Foti Division of Clinical Pathology University Hospital of Geneva Department of Cellular Physiology and Metabolism Faculty of Medicine University of Geneva Diabetes Center Faculty of Medicine University of Geneva Division of Gastroenterology and Hepatology University Hospital of Geneva

AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver ***: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical ***: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN imm

关键词： Fibrosis Phosphatase and tensin homolog Steatosis Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Alcoholic liver disease Cirrhosis Hepatocellular carcinoma

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Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease

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World Journal of Hepatology 2018年第1期10卷 73-81页

作者： Sophie Restellini Nicolas Goossens Sophie Clément Nicolas Lanthier Francesco Negro laura rubbia-brandt Laurent Spahr Department of Medical Specialties Division of Gastroenterology and Hepatology Geneva University Hospitals and University of Geneva Department of Genetic and Laboratory Medicine Division of Clinical Pathology Geneva University Hospitals and University of Geneva Laboratory of Gastroenterology and Hepatology Institut de Recherche Expérimentale et Clinique Université catholique de Louvain

AIM To explore the relationship between collagen proportionate area(CPA) and portal hypertension-related clinical manifestations in alcoholic liver disease(ALD).METHODS Retrospective study with chart review of patients with ALD adressed to our center between January 2012 and December 2013 for a transjugular liver biopsy(TJLB) and hepatic hemodynamic study. Patients were included if they met the following criteria:(1) Medical indication for a liver biopsy in the setting of ALD;(2) recent(< 15 d) clinical, radiological, endoscopic and biological data available; and(3) estimated follow-up of at least 6 mo. Liver tissue from cirrhotic subjects obtained from transjugular liver biopsies was stained with Picro Sirius red and computer-assisted digital image analysis to determine fibrosis density using CPA was performed. RESULTS We included 61 patients with alcoholic ALD, subdivided in 41 active alcohol drinkers and 20 durably abstinent patients. Nine healthy liver donors served as controls. Mean CPA in patients with ALD was 7.1%, with no difference between active drinkers and abstinent patients(P = 0.17). Using a fibrosis density cutoff of 5%, we observed a positive correlation between high fibrosis density and the hepatic venous pressure gradient(HVPG) only in active drinkers(P = 0.02). At 12-mo of follow-up, in the group of active alcohol drinkers, patients reaching a composite outcome showed a higher HVPG value as compared to those who did not(18.5 mm Hg vs 14.5 mm Hg P < 0.04) whereas CPA values were similar(6.9% vs 11%, P = 0.23).CONCLUSION In active alcoholic ALD, CPA correlates to portal pressure but only HVPG predicts clinical events, pointing to the role of alcohol as a modulator of portal hypertension.

关键词： Fibrosis Hepatic venous pressure gradient Cirrhosis Chronic advanced liver disease Collagen proportionate area

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Management of hepatocellular adenoma: Solitary-uncomplicated, multiple and ruptured tumors

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World Journal of Gastroenterology 2005年第36期11卷 5691-5695页

作者： Christian Toso Pietro Majno Axel Andres laura rubbia-brandt Thierry Berney Leo Buhler Philippe Morel Gilles Mentha Abdominal and Transplant Surgery University Hospital Geneva Switzerland Clinical Pathology University Hospital Geneva Switzerland

AIM： While hepatocellular adenomas （HAs） have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS： Twenty-five consecutive patients operated for solitary-uncomplicated （9）, multiple （6）, and ruptured （10） HAs were reviewed according to management strategies and outcomes. RESULTS： All solitary-uncomplicated HAs （ranged 2.2- 14 cm in size） were removed. Out of 25 HAs, 2 （8%） included loci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA （ranged 1.7-10 cm in size） were initially managed with hemodynamic support and angiography, allowing the embolizaUon of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d （range 4-70 d） after admission. CONCLUSION： Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery. 2005 The WJG Press and Elsevier Inc. All rights reserved

关键词： Liver Adenoma Management Surgery

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胰岛素抵抗与非糖尿病慢性丙型肝炎患者的肝纤维化有关

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世界核心医学期刊文摘（胃肠病学分册） 2005年第5期1卷 54-55页

作者： Muzzi A. Leandro G. rubbia-brandt L. 赵天智

Liver steatosis is a frequent finding in chronic hepatitis C. An association has been suggested between steatosis and fibrosis progression rate, but the pathogenetic mechanisms linking fatty infiltration and collagen deposition are unknown. We measured the levels of insulin resistance (as HOMA score) and leptin in 221 non-diabetic chronic hepatitis C patients, to assess their impact on liver steatosis and fibrosis, relative to other factors, using a multivariable logistic regression. When all 221 patients were considered, steatosis was associated with excessive alcohol intake, genotype 3, and serum HCV RNA level, whereas fibrosis was associated with HOMA score and age. In 152 patients infected with genotype non-3, steatosis was associated with alcohol abuse and HCV RNA level, and fibrosis with HOMA score and age. In the 69 patients with genotype 3, steatosis and fibrosis were associated with each other. The association between fibrosis and HOMA score held also when 22 obese patients were excluded from the analysis. Levels of insulin resistance were not correlated with the presence of steatosis. Thus, insulin resistance (but not leptin) may play a role in fibrogenesis in chronic hepatitis C patients infected with genotype non-3.

关键词：慢性丙型肝炎胰岛素抵抗肝纤维化丙型肝炎患者瘦素水平脂肪变性发病机制病毒感染胶原沉积脂肪浸润

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肝切除治疗八个或更多结肠癌肝脏转移灶

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肝胆外科杂志 2017年第3期25卷 167-167页

作者： Viganò LI Capussotti L Magno P Toso C Ferrero A De Rosa G rubbia-brandt L Mentha G Br J Surg 王石耿小平

背景：对于具有大量肝转移灶的结肠癌病人，手术切除可能是有效的治疗方法，但其确切的益处尚不清楚。方法从两个具有大样本容量的肝脏外科中心收集1998至2012年间施行手术切除的结肠癌肝转移的病人数据，并根据其转移灶的数量进行分组... 详细信息

背景：对于具有大量肝转移灶的结肠癌病人，手术切除可能是有效的治疗方法，但其确切的益处尚不清楚。方法从两个具有大样本容量的肝脏外科中心收集1998至2012年间施行手术切除的结肠癌肝转移的病人数据，并根据其转移灶的数量进行分组：组1（转移灶〈8），组2（转移灶≥8）。

关键词：结肠癌病人肝转移灶治疗方法肝脏外科肝切除手术切除病人数据样本容量

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