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chronic hepatitis c virus infection and lipoprotein metabolism

World Journal of Gastroenterology 2015年第36期21卷 10299-10313页

作者： Yoshio Aizawa Nobuyoshi Seki Tomohisa Nagano Hiroshi Abe Department of Internal Medicine The Jikei University Katsushika Medical Center

Hepatitis c virus(HcV) is a hepatotrophic virus and a major cause of chronic liver disease,including hepatocellular carcinoma,worldwide. The life cycle of HcV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides,free cholesterol,cholesteryl esters,and phospholipids are the major components of the transported lipids. The pathway of HcV assembly and secretion is closely linked to lipoprotein production and secretion,and the infectivity of HcV particles largely depends on the interaction of lipoproteins. Moreover,HcV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle,which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands,enzyme co-factors,and lipid transport carriers. Understanding the association between the life cycle of HcV and lipoprotein metabolism is important because each step of the life cycle of HcV that is associated with lipoprotein metabolism is a potential target for anti-HcV therapy. In this article,we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HcV with lipoprotein. Then,we review the outline of the processes of HcV assembly,secretion,and entry into hepatocytes,focusing on the association with lipoproteins. Finally,we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HcV infection with regard to abnormal apolipoproteins.

关键词： Hepatitis c virus Apolipoprotein Lipo-viral partic

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Retreatment with peginterferon and ribavirin in chronic hepatitis c

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World Journal of Gastroenterology 2015年第6期21卷 1994-1999页

作者： Yong Min Jo Sung Wook Lee Sang Young Han Yang Hyun Baek Soo Young Kim Woo Jae Kim Ji Hye Ahn Ji Young Lee Department of Internal Medicine Dong-A University School of Medicine

The development of boceprevir and telaprevir was a major step forward in the treatment of chronic hepatitis *** addition,the treatment of these infections has been recently revolutionized by the approval of sofosbuvir and ***,there are several challenges associated with the application of noveldrugs,such as new and more frequent adverse events,new drug interactions,and excessively high treatment *** additional concern is viral *** considerations highlight the fact that direct-acting antiviral agents are not a panacea and may not be the best option for all patients who are in need of *** retrospective study revealed that the sustained virologic response was not significantly reduced following peginterferon and ribavirin retreatment compared with the new *** suggest that patients who experience relapse shortly after completing treatment with peginterferon and ribavirin have a reasonable chance of achieving a sustained virologic response when retreated with these drugs alone.

关键词： chronic hepatitis c Direct-acting antiviral agents

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chronic hepatitis c genotype 1 treatment roadmap for resource constrained settings

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World Journal of Gastroenterology 2015年第6期21卷 1972-1981页

作者： Seng Gee Lim Department of Gastroenterology and Hepa-tology Department of Medicine National University Health System Yong Loo Lin School of Medicine National University of Singapore

AIM:To use existing hepatitis c virus(HcV)antiviral therapies as access to new treatments is ***:A Pub Med search for randomised control trials or meta-analysis related to response-guided therapy of HcV genotype 1 patients was undertaken using pegylated interferon and ribavirin(PR),boceprevir(B)and telaprevir(T)and lead-in where responseguided therapy at TW4(TW4),8(TW8),10(TW10),or12(TW12)based on HcVRNA(+)or HcVRNA(-).Studies presented at major conferences were also *** necessary,a post-hoc analysis was performed.A response-guided management roadmap was created based on sustained virological response(SVR).RESULTS:Starting with PR,those with HcVRNA(-)at TW4 have>86%SVR,while those are HcVRNA(+)have 34%-41.7%***(-)TW4 patients can have 24 wk PR if HcVRNA<400000 IU/m ***,28 wk BPR has similar *** HcVRNA(+)at TW4,72 wk PR leads to 53%SVR,hence BPR is a better option,and if HcVRNA(-)by TW8,28 wk therapy is *** HcVRNA(+)at TW8,then HcVRNA should be checked at TW10 and *** TW12,HcVRNA≥100 IU/m L activates the stopping *** roadmap is applicable for treatment-na?ve,treatment failures and cirrhotic *** from an Asia Pacific early access boceprevir program confirmed the findings that HcVRNA(-)at TW4,or TW8 conferred>80%SVR,leading to the"80-80"***:Using a roadmap based on HcVRNA(-)at TW4 or TW8(the"80-80"rule),high SVR can be achieved,and guide the best choices for treatment,and also reduces drug exposure in poor responders.

关键词： chronic hepatitis c hepatitis c virus RNA Sustaine

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Modulation of host lipid metabolism by hepatitis c virus: role of new therapies

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World Journal of Gastroenterology 2015年第38期21卷 10776-10782页

作者： José A Del campo Manuel Romero-Gómez Digestive Diseases and CIBERehd Valme University Hospital

It is well established that hepatitis c virus(HcV) infection and replication relies on host lipid metabolism. HcV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides,circulating infective particles are associated with verylow-density lipoprotein. On the other hand,higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HcV infection,suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy(> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HcV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review,host genetic factors,viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

关键词： Hepatitis c virus Lipid metabolism Direct acting a

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Todos Santos small RNA symposium

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RNA BIOLOGY 2019年第11期16卷 1526-1530页

作者： Winkenbach, Lindsay P. Doser, Rachel Reed, Kailee J. Pasquinellie, Amy E. Phillips, carolyn M. claycomb, Julie M. Colorado State Univ Dept Biochem & Mol Biol Ft Collins CO 80523 USA Colorado State Univ Dept Biomed Sci Ft Collins CO 80523 USA Colorado State Univ Dept Biol Ft Collins CO 80523 USA Colorado State Univ Cell & Mol Biol Program Ft Collins CO 80523 USA Univ Calif San Diego Div Biol San Diego CA 92103 USA Univ Southern Calif Dept Biol Sci Los Angeles CA USA Univ Toronto Dept Mol Genet Toronto ON Canada

Worm biologists from the United States, canada, and the United Kingdom gathered at the colorado State University Todos Santos center in Baja california Sur, Mexico, April 3-5, 2019 for the Todos Santos Small RNA Symposium. Meeting participants, many of whom were still recovering from the bomb cyclone that struck a large swath of North America just days earlier, were greeted by the warmth and sunshine that is nearly ubiquitous in the sleepy seaside town of Todos Santos. With only 24 speakers, the meeting had the sort of laid-back vibe you might expect amongst the palm trees and ocean breeze of the Pacific coast of Mexico. The meeting started with tracing the laboratory lineages of participants. Not surprisingly, the most common parental lineages represented at the meeting were Dr. craig Mello, Dr. Gary Ruvkun, and Dr. Victor Ambros, whom, together with Dr. Andy Fire and Dr. David Baulcombe, pioneered the small RNA field. In sad irony, on the closing day of the meeting, participants were met with the news of Dr. Sydney Brenner's passing. By establishing the worm, caenorhabditis elegans, as a model system Dr. Brenner paved the way for much of the research discussed here.

关键词： Small RNA piRNA miRNA siRNA RNAi Argonaute P granule c elegans

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World Journal of Gastroenterology 2015年第13期21卷 4006-4013页

作者： Yuan-Yuan Zhang Hong-Bo chen Yin Xu Peng Huang Jie Wang Yun Zhang Rong-Bin Yu Jing Su Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical University Department of Infectious Diseases Jurong Peoples’ Hospital Department of General Practice Kangda CollegeNanjing Medical University Institute of Epidemiology and Microbiology the Institute of Military Medicine of Nanjing Command

AIM: To determine the association between rapid viral response and IL28 B, IL28 RA, IL10 RB and Mx A polymorphisms in the chinese Han ***: The study cohort consisted of 238 chronic hepatitis c patients treated with interferon(IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI Taq Man allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis c virus(HcV) RNA was detected at weeks 0, 4, 12 and 24 of ***: Only IL28 B rs12980275 was associated with treatment response in the chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype(additive model: adjusted OR = 0.43, 95%cI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load < 500 copies/m L(logrank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HcV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiveroperating characteristic curve was 0.726. cONcLUSION: IL28 B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in chinese Han patients with hepatitis c.

关键词： Hepatitis c virus Interferon Rapid viral response

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Immune and non-immune responses to hepatitis c virus infection

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World Journal of Gastroenterology 2015年第38期21卷 10739-10748页

作者： Jiaren Sun Ricardo Rajsbaum Min Kyung Yi Department of Microbiology and Immunology Institute for Human Infections and ImmunityUniversity of Texas Medical Branch

The host innate and adaptive immune systems are involved in nearly every step of hepatitis c virus(HcV) infection. In patients,the outcome is determined by a series of complex host-virus interactions,whether it is a natural infection or results from clinical intervention. Strong and persistent cD8+ and cD4+ T-cell responses are critical in HcV clearance,as well as cytokineinduced factors that can directly inhibit virus replication. Newly available direct-acting antivirals(DAAs) are very effective in viral clearance in patients. DAA treatment may further result in the down-regulation of programmed death-1,leading to rapid restoration of HcV-specific cD8+ T cell functions. In this review,we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development as well as to current efforts aimed at understanding the host innate responses against HcV infection. current theories on how the ubiquitin system and interferon-stimulated genes may affect HcV replication are also discussed.

关键词： Hepatitis c virus Hepatitis T cell Direct-acting a

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Serum vitamin D_3 does not correlate with liver fibrosis in chronic hepatitis c

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World Journal of Gastroenterology 2015年第39期21卷 11152-11159页

作者： Yan Ren Mei Liu Jing Zhao Feng Ren Yu chen Jun-Feng Li Jing-Yun Zhang Feng Qu Jin-Lan Zhang Zhong-Ping Duan Su-Jun Zheng Artificial Liver Center Beijing You An Hospital Capital Medical University Institute of Liver Diseases Beijing YouA n Hospital Capital Medical University State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

AIM: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive chinese patients with chronic hepatitis c(cHc).METHODS: From July 2010 to June 2011, we enrolled 122 cHc patients and 11 healthy controls from Dingxicity, Gansu Province, china. The patients were infected with Hepatitis c virus(HcV) during blood cell retransfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholineste rase, prothrom binactivity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HcV RNA levels were measured by real-time PcR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry.R E S U LT S : Serumlevels of 2 5(OH) D3 but not 24,25(OH)2D3 were significantly lower in cHc patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HcV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation ***: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive chi

关键词： Hepatitis c virus 25-Hydroxyvitamin D3 24,25-Dihyd

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Inhibition of serotonin transporter expression by c/EBPβ in LPS-activated macrophage cells (HD11)

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INNATE IMMUNITY 2015年第4期21卷 406-415页

作者： Zimmermann, Katrin van Phi, Valerie D. Brase, Angela Loc Phi-van Friedrich Loeffler Inst Inst Anim Welf & Anim Husb D-29223 Celle Germany Tech Univ Munich Klinikum Rechts Isar Inst Radiol D-80290 Munich Germany

Serotonin (5-hydroxytryptamine;5-HT) transporter (5-HTT) is involved in inflammation and the stress response. In this study, we examined the regulation of 5-HTT expression in macrophage HD11 cells in response to bacterial LPS. Long-term exposure of cells to LPS (6-18h) produced a decrease in 5-HTT mRNA expression. Accordingly, reduced 5-HTT activity measured by 5-HT uptake was also observed in LPS-treated HD11 cells. Moreover, LPS treatment, as well as co-transfection with an expression vector encoding the chicken ccAAT/enhancer binding protein beta (c/EBP), resulted in inhibition of 5-HTT promoter activity. Indeed, sequence analysis revealed several c/EBP binding motifs in the upstream region of the 5-HTT gene, which specifically interacted with c/EBP both in an invitro band shift assay and in living HD11 cells. The c/EBP binding was activated in cells treated with LPS. The role of c/EBP in LPS inhibition of 5-HTT expression was further confirmed by small interfering RNA interference, which demonstrated that knockdown of endogenous c/EBP attenuated the inhibition of 5-HTT expression in LPS-treated cells. Taken together, the results suggest that c/EBP plays a critical role in regulating the 5-HTT gene in macrophages in response to pro-inflammatory stimuli.

关键词： c EBP ss 5-HT HD11 cells LPS serotonin transporter

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Epidemiology of hepatitis c in croatia in the European context

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World Journal of Gastroenterology 2015年第32期21卷 9476-9493页

作者： Tatjana Vilibic-cavlek Jasmina Kucinar Bernard Kaic Maja Vilibic Nenad Pandak Ljubo Barbic Vladimir Stevanovic Jasmina Vranes Department of Virology Croatian National Institute of Public Health and School of Medicine University of Zagreb Department of Microbiology Istria County Institute of Public Health Department of Epidemiology Croatian National Institute of Public Health Vrapce University Psychiatric Hospital Department of Infectious Diseases General Hospital "Dr Josip Bencevic" School of Medicine University of Osijek Department of Microbiology and Infectious Diseases with Clinic Faculty of Veterinary Medicine University of Zagreb Department of Microbiology Public Health Institute "Dr Andrija Stampar" and School of Medicine University of Zagreb

We analyzed prevalence, risk factors and hepatitis c virus(HcV) genotype distribution in different population groups in croatia in the context of HcV epidemiology in Europe, with the aim to gather all existing information on HcV infection in croatia which will be used to advise upon preventive measures. It is estimated that 35000-45000 of the croatian population is chronically infected with HcV. Like in other European countries, there have been changes in the HcV epidemiology in croatia over the past few decades. In some risk groups(polytransfused and hemodialysis patients), a significant decrease in the HcV prevalence was observed after the introduction of routine HcV screening of blood/blood products in 1992. Injecting drug users(IDUs) still represent a group with the highest risk for HcV infection with prevalence ranging from 29% to 65%. compared to the prevalence in thecroatian general population(0.9%), higher prevalence rates were found in prison populations(8.3%-44%), human immunodeficiency virus-infected patients(15%), persons with high-risk sexual behavior(4.6%) and alcohol abusers(2.4%). Low/very low prevalence was reported in children and adolescents(0.3%) as well as in blood donors(0%-0.009%). In addition, distribution of HcV genotypes has changed due to different routes of transmission. In the general population, genotypes 1 and 3 are most widely distributed(60.4%-79.8% and 12.9%-47.9%, respectively). The similar genotype distribution is found in groups with high-risk sexual behavior. Genotype 3 is predominant in croatian IDUs(60.5%-83.9%) while in the prison population genotypes 3 and 1 are equally distributed(52.4% and 47.6%). Data on HcV prevalence and risk factors for transmission are useful for implementation of preventive measures and HcV screening.

关键词： Hepatitis c Seroprevalence Genotypes croatia Europ

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