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Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei
Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts' mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups...
January 17, 2018: Scientific Reports
Tianbin Chen, Zhen Xun, Jinpiao Lin, Ya Fu, Wennan Wu, Xiaochun Fu, Yuhai Hu, Yongbin Zeng, Qishui Ou
Recent studies have demonstrated a potential link between mitochondrial DNA (mtDNA) content and cirrhosis or hepatocellular carcinoma (HCC). However, there are few studies evaluating mtDNA content as a noninvasive marker of chronic hepatitis B infection (CHB). In this study, we conducted a case-control study to determine mtDNA content in peripheral blood leukocyte (PBL) samples from 76 CHB cases naïve to antivirus therapy and 96 healthy controls, and then evaluated the association between mtDNA content and baseline serum concentration of HBV markers...
November 2017: Journal of Medical Virology
Giordano Madeddu, Silvia Ortu, Giovanni Garrucciu, Ivana Maida, Michela Melis, Alberto Augusto Muredda, Maria Stella Mura, Sergio Babudieri
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...
July 2017: Journal of Medical Virology
Ling Li, Hie-Won Hann, Shaogui Wan, Richard S Hann, Chun Wang, Yinzhi Lai, Xishan Ye, Alison Evans, Ronald E Myers, Zhong Ye, Bingshan Li, Jinliang Xing, Hushan Yang
Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model...
April 11, 2016: Scientific Reports
Li Zhou, Xiaoyu Liu, Feng Ren, Yu Chen, Sujun Zheng, Yuanping Han, Caiyan Zhao, Zhongping Duan
BACKGROUND: This study aimed to assess whether long-term entecavir monotherapy induces mitochondrial toxicity in patients with chronic hepatitis B (CHB). MATERIAL AND METHODS: This was a prospective study in 34 antiviral treatment-naïve patients with CHB who received entecavir monotherapy and were followed up for 4 years. Blood samples were collected after 0, 2, 3, and 4 years of entecavir (ETC) monotherapy (ETC0, ETC2, ETC3, and ETC4, respectively). Mitochondrial DNA (mtDNA) contents were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and mtDNA4977 depletions were detected using nested PCR...
2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Chun Wang, Hie-Won Hann, Richard S Hann, Shaogui Wan, Ronald E Myers, Zhong Ye, Jinliang Xing, Hushan Yang
BACKGROUND AND AIMS: Accumulating evidence has indicated that variations of mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular carcinoma (HCC). However, no study has been conducted to evaluate the association of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of HCC. METHODS: We conducted a nested case-control study including 136 cirrhotic hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV controls...
June 2015: Digestive Diseases and Sciences
Yoon-Ok Jang, Xianglan Quan, Ranjan Das, Shanhua Xu, Choon-Hee Chung, Chan Mug Ahn, Soon-Koo Baik, In Deok Kong, Kyu-Sang Park, Moon Young Kim
BACKGROUND: Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E...
2012: BMC Gastroenterology
Geum-Youn Gwak, Dong Ho Lee, Tae Gun Moon, Moon Suk Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Jae-Won Joh, Byung Chul Yoo
BACKGROUND/AIMS: We investigated the correlation of HBV pre-S mutation with the sites and frequencies of mtDNA mutations in HCC patients. METHODOLOGY: Twenty-seven HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed. Direct sequencing of the mtDNA D-loop was performed in paired HCC and adjacent non-neoplastic liver tissues. The common 4977 bp deletion of miDNA was examined by PCR...
March 2011: Hepato-gastroenterology
Pinghu Zhang, Luyong Zhang, Zhenzhou Jiang, Yating Xiong, Hongkui Chen, Yuanqing Tao, Maozhi Hu, Zhan Li
Metacavir (PNA) is a novel synthetic nucleoside analogue for the treatment of hepatitis B virus (HBV). Our recent studies showed that PNA, a prodrug of 2',3'-dideoxyguanosine (ddG), exhibited lower mitochondrial toxicity in long-term cultures of HepG2 cells. In the current study, we examined the long-term effects of PNA on mitochondrial toxicity in Marmota himalayana (Himalayan marmot). Himalayan marmots were treated daily with oral PNA (50 or 100 mg/kg), ziduvidine (AZT) (100 mg/kg), or water (control) for 90 days...
May 2011: Antimicrobial Agents and Chemotherapy
Ruixing Zhang, Fengbin Zhang, Cuiju Wang, Shunxiang Wang, Yih-Horng Shiao, Zhanjun Guo
BACKGROUND: Hepatocellular carcinoma (HCC) is frequently preceded by hepatitis virus infection or alcohol abuse. Genetic backgrounds may increase susceptibility to HCC from these exposures. METHODS: Mitochondrial DNA (mtDNA) of peripheral blood, tumor, and/or adjacent non-tumor tissue from 49 hepatitis B virus-related and 11 alcohol-related HCC patients, and from 38 controls without HCC were examined for single nucleotide polymorphisms (SNPs) and mutations in the D-Loop region...
September 18, 2010: Journal of Experimental & Clinical Cancer Research: CR
Pinghu Zhang, Luyong Zhang, Zhenzhou Jiang, Tao Wang, Hongkui Chen, Yating Xiong, Zhan Li
Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog for oral administration with potent and specific antiviral activity against hepatitis B virus (HBV). We assessed the potential for mitochondrial toxicity of PNA in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and the activities of respiratory-chain complexes I to IV...
November 2010: Antimicrobial Agents and Chemotherapy
Patrick Ingiliz, Marc-Antoine Valantin, Claudine Duvivier, Fadia Medja, Stephanie Dominguez, Frédéric Charlotte, Roland Tubiana, Thierry Poynard, Christine Katlama, Anne Lombès, Yves Benhamou
UNLABELLED: Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR)...
February 2009: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Charles E Mazzucco, Robert K Hamatake, Richard J Colonno, Daniel J Tenney
Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of chronic hepatitis B virus (HBV) infection that exhibits potent activity against viral reverse transcriptase. We assessed the potential for mitochondrial toxicity of ETV in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and levels of mitochondrial proteins COX II and COX IV...
February 2008: Antimicrobial Agents and Chemotherapy
M Pinti, L Troiano, M Nasi, R Ferraresi, J Dobrucki, A Cossarizza
Currently, drugs have been synthesised that can significantly delay the course of several viral infections, including those provoked by HBV, HCV or HIV, but that display consistent side effects, including toxicity for organelles such as mitochondria. Several in vitro models and techniques have been developed to analyse the effects of such compounds. HepG2 cells (from human hepatoma) are an excellent model to investigate mitochondrial (mt) toxicity because of their high content of organelles and mtDNA, and actually different investigators are indeed using such cells...
April 2003: Journal of Biological Regulators and Homeostatic Agents
Jin-Ming Wu, Ju-Sheng Lin, Na Xie, Kuo-Huan Liang
AIM: To explore the inhibition of beta-L-D4A on hepatitis B virus (HBV) in 2.2.15 cells derived from HepG2 cells transfected with HBV genome. METHODS: 2.2.15 cells were plated at a density of 5X104 per well in 12-well tissue culture plates, and treated with various concentrations of beta-L-D4A for 6 days. In the end, 5 microl of medium was used for the estimation of HBsAg and HBeAg, the other medium was processed to obtain virions by a polyethylene glycol precipitation method...
August 2003: World Journal of Gastroenterology: WJG
G Birkus, C S Gibbs, T Cihlar
Adefovir is a potent nucleotide analog inhibitor of hepatitis B virus (HBV) DNA polymerase. Its oral prodrug adefovir dipivoxil has been approved for the treatment of chronic HBV infection. In this study, adefovir was characterized for its in vitro effects on mitochondrial DNA (mtDNA) synthesis and compared with the nucleoside analogues lamivudine (3TC), fialuridine (FIAU), and zalcitabine (ddC). No substantial changes in mtDNA content were detected in human hepatoblastoma HepG2 cells and normal human skeletal muscle cells following a 9-day treatment with 0...
January 2003: Journal of Viral Hepatitis
X Hu, A Javadian, P Gagneux, B H Robertson
The surface antigen gene region from five chronic hepatitis B virus (HBV) infected chimpanzees was amplified by PCR and the sequence determined. Sequence comparison confirmed that all of the sequences were chimpanzee hepatitis B virus (chHBV) and they appeared to represent three distinct clusters or branches. To address the question of whether the three branches represented recently identified subspecies of chimpanzees, we determined the sequence of the mitochondrial DNA hypervariable D loop from hair samples obtained from these five chimpanzees...
November 5, 2001: Virus Research
L Cui, R F Schinazi, G Gosselin, J L Imbach, C K Chu, R F Rando, G R Revankar, J P Sommadossi
A group of enantiomeric nucleoside analogues with beta-D or beta-L configuration, which represent potential candidates for the treatment of hepatitis B virus (HBV) infection, were incubated in human hepatoblastoma HepG2 cells at concentrations between 0.1 and 10 microM for 4-14 days. Then the effect on mitochondrial DNA (mtDNA) content, lactic acid production, lipid droplet formation, and mitochondrial morphology were evaluated. No effect on lactic acid production was detected in cells treated with beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-L-FTC), beta-D-2',3'-dideoxy-5-fluoro-3'-thiacytidine (beta-D-FTC), racemic cis 2',3'-dideoxy-5-fluoro-3'thiacytidine [(+/-)-FTC], and 2,4-diamino-7-(2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl) pyrrolo[2',3'-d]pyrimidine (T70178), whereas a slight increase was associated with beta-D-2-hydroxymethyl-5-(2,6-diaminopurin-9-yl)-1,3-dixolane++ + (beta-D-DAPD) and 4-amino-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimi dine -5-thiocarboxamide (T70182) at 10 microM...
November 22, 1996: Biochemical Pharmacology
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