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Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

World Journal of Gastroenterology 2017年第30期23卷 5499-5507页

作者： frederik Temmerman Feng Chen Louis Libbrecht Ingrid Vander Elst Petra Windmolders Yuanbo Feng Yicheng Ni Humbert De Smedt frederik nevens Jos van Pelt Laboratory of Hepatology Department of Clinical and Experimental Medicine Faculty of Medicine University of Leuven Department of Gastroenterology and Hepatology University Hospitals KU Leuven Department of Radiology The first Affiliated Hospital School of Medicine Zhejiang University Department of Pathology Ghent University Hospital Department of Imaging and Pathology Faculty of Medicine Laboratory of Molecular and Cellular Signalling Unit of Clinical Digestive Oncology Department of Oncology KU Leuven and Leuven Cancer Institute (LKI)

AIM To develop a MRI-based method for accurate determination of liver volume(LV) and to explore the effect of long-term everolimus(EVR) treatment on LV in PCK rats with hepatomegaly. METHODS Thirty-one female PCK rats(model for polycystic-liverdisease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly(comparable to what is done in the human disease). Animals received: controls(n = 14), lanreotide(LAN: 3 mg/kg per 2 wk)(n = 10) or everolimus(EVR: 1 mg/kg per day)(n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene(quantitative RT-PCR) and protein expression(by Western blot) of the PI3K/Ak T/m TOR signaling pathway was investigated. RESULTS LV determination by MRI correlated excellent with the ex vivo measurements(r = 0.99, P < 0.001). The relative changes in LV at the end of treatment were:(controls) +31.8%;(LAN) +5.1% and(EVR) +8.8%, indicating a significantly halt of LV progression compared with controls(respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis(P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt(Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/Ak T/m TOR signaling cascade but acting at different molecular *** Everolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. m TORinhibition should be further explored in PCLD patients especially those that need immunosuppression.

关键词： Fibrocystic liver disease mTOR inhibitor somatostatin analogue liver volume measurement Magnetic resonance imaging

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Early prediction of major depression in chronic hepatitis C patients during peg-interferon α-2b treatment by assessment of vegetative-depressive symptoms after four weeks

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World Journal of Gastroenterology 2007年第43期13卷 5736-5740页

作者： Geert Robaeys Jozef De Bie Marieke C Wichers Liesbeth Bruckers frederik nevens Peter Michielsen Marc Van Ranst Frank Buntinx Department of Gastroenterology and Hepatology Ziekenhuis Oost Limburg Genk Belgium Department of Psychiatry Ziekenhuis Oost Limburg Genk Belgium Department of Psychiatry and Neuro-psychiatry South Limburg Mental Health Research and Teaching Network EURON Maastricht University Maastricht The Netherlands Center for Statistics Limburgs Universitair Centrum Diepenbeek Belgium Department of Hepatology Katholieke Universiteit Leuven Leuven Belgium Division of Gastroenterology and Hepatology University Hospital Antwerp Belgium Laboratory of Clinical and Epidemiological Virology Department of Microbiology and Immunology Rega Institute and University Hospitals Katholieke Universiteit Leuven Leuven Belgium Department of General Practice Katholieke Universiteit Leuven Leuven Belgium and Department of General Practice Maastricht University The Netherlands

AIM: To study the predictive value of the vegetative- depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon α-2b of chronic hepatitis C (CHC) patients. METHODS: The predictive value of vegetative- depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi- center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. RESULTS: Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). CONCLUSION: In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetativedepressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results.

关键词： Interferons Hepatitis C Chronic Substance-related disorders Depression Zung self rating scale Prognosis

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