circulating micrornas in patients with chronic hepatitis c and non-alcoholic fatty liver disease循环microrna在慢性丙型肝炎患者和非酒精脂肪肝疾病.pdfVIP

Circulating MicroRNAs in Patients with Chronic Hepatitis C and Non-Alcoholic Fatty Liver Disease 1 1,2 3 4 1 Silvia Cermelli , Anna Ruggieri , Jorge A. Marrero , George N. Ioannou , Laura Beretta * 1 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Department of Infectious, Parasitic and ` Immune-Mediated Disease, Istituto Superiore di Sanita, Roma, Italy, 3 Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America, 4 Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington, United States of America Abstract MicroRNAs miR-122, miR-34a, miR-16 and miR-21 are commonly deregulated in liver fibrosis and hepatocellular carcinoma. This study examined whether circulating levels of these miRNAs correlate with hepatic histological disease severity in patients with chronic hepatitis C infection (CHC) or non-alcoholic fatty-liver disease (NAFLD) and can potentially serve as circulating markers for disease stage assessment. We first used an in vitro model of hepatitis C virus (HCV) infection to measure the extracellular levels of these four miRNAs. Whereas miR-21 extracellular levels were unchanged, extracellular levels of miR-122, miR-34a and to a lesser extent miR-16, steadily increased during the course of HCV infection, independently of viral replication and production. Similarly, in CHC patients, serum levels of miR-122, miR-34a and miR-16 were sign