{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:31:19Z","timestamp":1789669879993,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Inhibition of viral replication is the most important goal in patients with Hepatitis B virus chronic infection (CHB). Currently, five oral nucleo(t)side analogs (NAs), including Lamivudine, Adefovir, Telbivudine, Entecavir, and Tenofovir, have been approved for treatment. The widespread use of NAs has also been linked with a progressive growth of unlikely anomaly attributable to mitochondrial dysfunctions, not previously recognized. Here, we explore the hypothesis that NAs may cause persistent epigenetic changes during prolonged NAs therapy in CHB patients. We obtained peripheral blood mononuclear cells (PBMC) from whole blood samples of consecutive patients with chronic HBV infection, 18 receiving NAs and 20 untreated patients. All patients were Caucasian and Italians. Epigenetic analysis was performed by Bisulphite sequencing PCR to search the existence of methylated cytosine residues in the Light (L)\u2010strands of mitochondrial DNA control region (D\u2010loop). Gene expression analysis of DNA methyltransferases 1 was performed by a quantitative relative Real\u2010Time Polymerase Chain Reaction (PCR). DNMT1 expression was significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009000001) higher in NA treated patients (4.09, IQR 3.52\u20105.15) when compared with HBV naives (0.61, IQR 0.34\u20100.82). Besides, DNMT1 expression was significantly correlated with NA therapy duration (Spearman Rho\u2009=\u20090.67; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Furthermore, NA therapy duration was the only significant predictor of DNMT1 expression at multivariate analysis (Beta\u2009=\u20090.95, <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.0000001). Bisulphite PCR sequencing showed that methylation of cytosine residues occurred in a higher percentage in patients treated with NAs in comparison with untreated patients and healthy controls. Our data showed a DNMT1 overexpression significantly correlated to NA therapy duration and an higher regional mtDNA hypermethylation. This might suggest an epigenetic alteration that could be involved in one of the possible mechanisms of mitochondrial gene regulation during NAs therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24742","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T10:59:11Z","timestamp":1481021951000},"page":"1208-1214","source":"Crossref","is-referenced-by-count":7,"title":["DNMT1 modulation in chronic hepatitis B patients and hypothetic influence on mitochondrial DNA methylation status during long\u2010term nucleo(t)side analogs therapy"],"prefix":"10.1002","volume":"89","author":[{"given":"Giordano","family":"Madeddu","sequence":"first","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ortu","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Garrucciu","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Clinical and Experimental Medicine University Hospital Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Maida","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Melis","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Augusto","family":"Muredda","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Stella","family":"Mura","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Babudieri","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases Department of Clinical and Experimental Medicine University of Sassari Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i20.6262"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i19.5730"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr388"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v6.i5.284"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)07219-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)06102-4"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.1.101"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22885"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3028"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0954422411000138"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2012.07.002"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-13-0178"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00314.2006"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.2174\/138161211796904731","article-title":"Mithocondrial toxicity in HAART: an overview of in vitro evidence","volume":"17","author":"Apostolova N","year":"2011","journal-title":"Curr Pharm Des"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr232"},{"key":"e_1_2_6_17_1","unstructured":"GarlickKT. 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