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Karin Krebs, Nina Böttinger, Li-Rung Huang, Markus Chmielewski, Silke Arzberger, Georg Gasteiger, Clemens Jäger, Edgar Schmitt, Felix Bohne, Michaela Aichler, Wolfgang Uckert, Hinrich Abken, Mathias Heikenwalder, Percy Knolle, Ulrike Protzer
BACKGROUND & AIMS: Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage...
August 2013: Gastroenterology
Woohyun Kim, Sooyoung Lee, Yeongnam Son, Chunkyu Ko, Wang-Shick Ryu
: HBx, a small regulatory protein of hepatitis B virus (HBV), augments viral DNA replication by stimulating viral transcription. Among numerous reported HBx-binding proteins, DDB1 has drawn attention, because DDB1 acts as a substrate receptor of the Cul4-DDB1 ubiquitin E3 ligase. Previous work reported that the DDB1-HBx interaction is indispensable for HBx-stimulated viral DNA replication, suggesting that the Cul4-DDB1 ubiquitin E3 ligase might target cellular restriction factors for ubiquitination and proteasomal degradation...
November 1, 2016: Journal of Virology
Massimo Levrero, Barbara Testoni, Fabien Zoulim
Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini-chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss±anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status...
June 2016: Current Opinion in Virology
Mohsin Khan, Gulam Hussain Syed, Seong-Jun Kim, Aleem Siddiqui
Hepatitis B virus (HBV) suppresses innate immune signaling to establish persistent infection. Although HBV is a DNA virus, its pre-genomic RNA (pgRNA) can be sensed by RIG-I and activates MAVS to mediate interferon (IFN) λ synthesis. Despite of the activation of RIG-I-MAVS axis by pgRNA, the underlying mechanism explaining how HBV infection fails to induce interferon-αβ (IFN) synthesis remained uncharacterized. We demonstrate that HBV induced parkin is able to recruit the linear ubiquitin assembly complex (LUBAC) to mitochondria and abrogates IFN β synthesis...
June 2016: PLoS Pathogens
Danbi Lee, Heather Lyu, Young-Hwa Chung, Jeong A Kim, Priya Mathews, Elizabeth Jaffee, Lei Zheng, Eunsil Yu, Young Joo Lee, Soo Hyung Ryu
AIM: To determine the genomic changes in hepatitis B virus (HBV) and evaluate their role in the development of hepatocellular carcinoma (HCC) in patients chronically infected with genotype C HBV. METHODS: Two hundred and forty chronic hepatitis B (CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced using the direct sequencing method...
June 21, 2016: World Journal of Gastroenterology: WJG
Shih-Hao Young, Tien-Hsin Wei, Chung-Chi Lin, Chi-Jen Chu, Fa-Yauh Lee, May-Ing Yu, Rei-Hwa Lu, Chiao-Yu Chang, Pei-Ling Yang, Mei-Hui Wang, Han-Chieh Lin
Reactivation of hepatitis B virus (HBV) infection is common (~20-50%) during cancer chemotherapy. Baseline HBV replication status is an important risk factor for HBV reactivation. To date, data on the baseline HBV DNA level for chronic hepatitis B (CHB) patients prior to chemotherapy, particularly for non-hematological malignancies, are limited. A total of 105 consecutive CHB patients with solid tumors who received prophylactic antiviral therapy prior to chemotherapy from November, 2011 to December, 2014, were enrolled in this study...
July 2016: Molecular and Clinical Oncology
Fabien Zoulim, Fanny Lebossé, Massimo Levrero
Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) and although a prophylactic vaccine and effective antiviral therapies are available, no cure exists. Curative regimens are urgently needed because up to one million deaths per year are caused by HBV-related liver cancer and end-stage liver disease. HBV is an hepatotropic virus which belongs to the Hepadnaviridae family and replicates its DNA genome via a reverse transcriptase mechanism. Effective therapies have been developed for chronic hepatitis B (CHB) infection in the last two decades...
June 2016: Current Opinion in Virology
Zong-Sheng Tang, You-Hua Hao, E-Juan Zhang, Chun-Li Xu, Yun Zhou, Xin Zheng, Dong-Liang Yang
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects...
August 2016: Molecular Medicine Reports
Jörg Petersen, Alexander J Thompson, Massimo Levrero
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide. Currently available antiviral treatment options for chronic hepatitis B include pegylated interferon alpha2a (PegIFN) or nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of sustained on-treatment response to therapy. The advantages of PegIFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post-treatment response to therapy...
October 2016: Journal of Hepatology
Zongguo Yang, Liping Zhuang, Yunfei Lu, Qingnian Xu, Bozong Tang, Xiaorong Chen
Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5...
March 15, 2016: Oncotarget
Hai-Jun Li, Nai-Cui Zhai, Hong-Xiao Song, Yang Yang, An Cui, Tian-Yang Li, Zheng-Kun Tu
Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum...
December 28, 2015: Journal of Clinical and Translational Hepatology
Betty L Slagle, Michael J Bouchard
The efficient replication of hepatitis B virus (HBV) requires the HBV regulatory hepatitis B virus X (HBx) protein. The exact contributions of HBx are not fully understood, in part because of the limitations of the assays used for its study. When HBV replication is driven from a plasmid DNA, the contribution of HBx is modest. However, there is an absolute requirement for HBx in assays that recapitulate the infectious virus life cycle. There is much evidence that HBx can contribute directly to HBV replication by acting on viral promoters embedded within protein coding sequences...
March 2016: Cold Spring Harbor Perspectives in Medicine
Slim Fourati, Razvan Cristescu, Andrey Loboda, Aarthi Talla, Ali Filali, Radha Railkar, Andrea K Schaeffer, David Favre, Dominic Gagnon, Yoav Peretz, I-Ming Wang, Chan R Beals, Danilo R Casimiro, Leonidas N Carayannopoulos, Rafick-Pierre Sékaly
Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine...
2016: Nature Communications
Tianyu He, Jidong Jia
Universal HBV vaccination in infants has led to a dramatic decline of HBsAg prevalence in many parts of the world, but the positive rate of HBsAg in women of childbearing age is still high in endemic areas. Antiviral therapy during pregnancy may be indicated to control the liver disease of the mother or to prevent the MTCT. The decision on initiation, switching, continuation or stopage of the antiviral therapy should be made after careful consideration of the benefit and risk to both mothers and foetuses. For prepregnant women of childbearing age, a finite course of interferon is preferred if a pregnancy in the distant future is planned, whereas safer NAs could be started if a pregnancy in the near future is desired...
January 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Federica Invernizzi, Mauro Viganò, Glenda Grossi, Pietro Lampertico
Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis...
January 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Jiannis Vlachogiannakos, George V Papatheodoridis
Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40 years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC)...
January 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Chih-Lin Lin, Hung-Chih Yang, Jia-Horng Kao
Current antiviral therapies have dramatically improved the long-term outcomes of patients with chronic hepatitis B virus (HBV) infection. Both interferon (IFN) and nucleos(t)ide analogue (NA) treatments have been shown to reduce the progression of liver disease in chronic hepatitis B (CHB) patients. However, persistent covalently closed circular DNA (cccDNA) can result in a viral relapse after discontinuation of antiviral treatment. On the basis of extensive research on the HBV lifecycle and virus-host interactions, several new agents focusing on viral and host targets are under development to cure HBV...
January 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Michelle Martinot-Peignoux, Patrick Marcellin
Molecular biology techniques are routinely used to diagnose and monitor treatment in patients with chronic hepatitis B (CHB). These tools can detect and quantify viral genomes and analyse their sequences to determine genotype. The increasing use of these tools to monitor patients has greatly improved the management of CHB infection by maximizing the potential for individualized treatment. HBV genotyping has become increasingly important and provides additional information to predict a response to therapy. More sensitive methods to determine HBV DNA levels are now available and the units of measurements have been standardized...
January 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Andrea Caballero, Josep Gregori, Maria Homs, David Tabernero, Carolina Gonzalez, Josep Quer, Maria Blasi, Rosario Casillas, Leonardo Nieto, Mar Riveiro-Barciela, Rafael Esteban, Maria Buti, Francisco Rodriguez-Frias
This study assesses the presence and outcome of genotype mixtures in the polymerase/surface and X/preCore regions of the HBV genome in patients with chronic hepatitis B virus (HBV) infection. Thirty samples from ten chronic hepatitis B patients were included. The polymerase/surface and X/preCore regions were analyzed by deep sequencing (UDPS) in the first available sample at diagnosis, a pre-treatment sample, and a sample while under treatment. HBV genotype was determined by phylogenesis. Quasispecies complexity was evaluated by mutation frequency and nucleotide diversity...
2015: PloS One
Mihai Voiculescu
Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases...
December 2015: Journal of Gastrointestinal and Liver Diseases: JGLD
2016-07-20 00:22:23
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