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Virus C and liver transplantation

Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
Lara Danziger-Isakov, William J Steinbach, Grant Paulsen, Flor M Munoz, Leigh R Sweet, Michael Green, Marian G Michaels, Janet A Englund, Alastair Murray, Natasha Halasa, Daniel E Dulek, Rebecca Pellett Madan, Betsy C Herold, Brian T Fisher
Background: Respiratory virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear. Methods: A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant...
March 10, 2018: Journal of the Pediatric Infectious Diseases Society
O El-Sherif, Z G Jiang, E B Tapper, K C Huang, A Zhong, A Osinusi, M Charlton, M Manns, N H Afdhal, K Mukamal, J McHutchison, D M Brainard, N Terrault, M P Curry
BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce model for end-stage liver disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus (HCV). However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials of the effects of sofosbuvir-based therapy in patients with HCV-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C)...
March 10, 2018: Gastroenterology
Gulziya Ismailova, Eugene Yenin, Shokan Kaniev, Dinara Bayguisova, Talgat Tajibaev
OBJECTIVES: Hepatocellular carcinoma is the predominant malignancy in patients with cirrhosis and chronic liver disease. Our aim was to assess the morphologic, radiologic, and immunologic charac teristics of hepatocellular carcinoma and liver cirrhosis concerning surgical treatment tactics. MATERIALS AND METHODS: We performed a cross-sectional analysis of a prospective study performed at the JSC National Scientific Center of Surgery (named after A. Syzganov). The study included 58 patients: 31 with hepatocellular carcinoma (53...
March 2018: Experimental and Clinical Transplantation
Karoly Toth, Jacqueline F Spencer, Baoling Ying, Ann E Tollefson, Caroll B Hartline, Eric T Richard, Jiajun Fan, Jinglei Lyu, Boris A Kashemirov, Cheryl Harteg, Dawn Reyna, Elke Lipka, Mark N Prichard, Charles E McKenna, William S M Wold
Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, AdV can cause serious infection in severely immunosuppressed individuals, especially pediatric patients undergoing allogeneic hematopoietic stem cell transplantation, where mortality rates are up to 80% with disseminated disease. Despite the seriousness of AdV disease, there are no drugs approved specifically to treat AdV infections. We report here that USC-087, an N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analog of cidofovir, is highly effective against multiple AdV types in cell culture...
March 3, 2018: Antiviral Research
Anand Rattansingh, Hosein Amooshahi, Ravi J Menezes, Florence Wong, Sandra Fischer, Richard Kirsch, Mostafa Atri
OBJECTIVE: To determine the accuracy of shear-wave elastography (SWE) to differentiate low from advanced degrees of liver fibrosis in hepatitis C patients. MATERIAL & METHOD: Consented native/transplant hepatitis C patients underwent SWE using a C1-6 MHz transducer before ultrasound (US)-guided liver biopsy. Five interpretable SWE samples were obtained from the right lobe of the liver immediately before US-guided random biopsy of the right lobe. Average kilopascal (kPa) values were compared to the meta-analysis of histological data in viral hepatitis (METAVIR) fibrosis grading...
March 6, 2018: Journal of Clinical Ultrasound: JCU
L Ryom, C Boesecke, M Bracchi, J Ambrosioni, A Pozniak, J Arribas, G Behrens, Pgm Mallon, M Puoti, A Rauch, J M Miro, O Kirk, C Marzolini, J D Lundgren, M Battegay
BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. GUIDELINE HIGHLIGHTS: Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management...
March 1, 2018: HIV Medicine
Melisa Dirchwolf, Sebastián Marciano, Diego H Giunta, Maria L Posadas-Martínez, Scott W Biggins, Andrés E Ruf
BACKGROUND: Hepatitis C virus (HCV) related cirrhosis is a leading indication for liver transplantation (LT) worldwide. Access to effective HCV treatment is inequitable globally. We aimed to analyze whether the introduction of effective HCV treatment caused an impact in LT trends in a middle-income country. METHODS: Cross sectional analysis of all adult patients who were listed/received a LT in Argentina for HCV, alcohol-related liver disease (ALD) or autoimmune hepatitis/primary biliary cirrhosis (AIH/PBC) from 2007 to 2017...
February 27, 2018: Clinical Transplantation
S Garcia-Madrona, I Corral-Corral
INTRODUCTION: Occipital condyle syndrome consists of the presence of unilateral occipital headache exacerbated by moving the head and is accompanied by paralysis of the ipsilateral hypoglossal nerve. One of its causes is infiltration of the base of the skull by bone metastases, especially those affecting the hypoglossal nerve due to infiltration as it passes through the osseous canal. CASE REPORTS: We report two clinical cases of occipital condyle syndrome secondary to metastatic hepatocarcinoma...
March 1, 2018: Revista de Neurologia
Ralf Bartenschlager, Thomas F Baumert, Jens Bukh, Michael Houghton, Stanley M Lemon, Brett D Lindenbach, Volker Lohmann, Darius Moradpour, Thomas Pietschmann, Charles M Rice, Robert Thimme, Takaji Wakita
The development and clinical implementation of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C. Infection with any viral genotype can now be eliminated in more than 95% of patients with short courses of all-oral, well-tolerated drugs, even in those with advanced liver disease and liver transplant recipients. DAAs have proven so successful that some now consider hepatitis C virus (HCV) amenable to eradication, and continued research on the virus of little remaining medical relevance...
February 22, 2018: Virus Research
P N Brennan, M C Donnelly, K J Simpson
BACKGROUND: A significant proportion of cases of acute liver failure (ALF) do not have an identifiable cause; so called "non A-E," "non A, non B, non C," "seronegative" or "indeterminate" hepatitis. However, this entity is clinically not well described. AIM: To collate the known incidence and outcomes in indeterminate hepatitis. This systematic review sought to identify potential aetiologies that ought to be considered, and identify likely future objectives in classification and treatment strategies for indeterminate hepatitis...
February 21, 2018: Alimentary Pharmacology & Therapeutics
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ATP binding cassette subfamily B member 4 gene (ABCB4 or MDR2) locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin 17 (IL17), yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells...
February 15, 2018: Gastroenterology
Pierluigi Toniutto
Although clinical guidelines provide clear indications on the treatment of patients with chronic HCV related liver disease, there are still clinical situations in which clinicians experience and judgment remain essential in the proper patient management. These are mainly represented by antiviral therapy in patients with decompensated liver disease, especially if they are candidates for liver transplantation or with significant comorbidities and complex pharmacological therapies. Antiviral retreatment of patients who failed a regimen containing an NS5A protease inhibitor still appears to be a delicate context in which no solid recommendations are provided, especially in patients with HCV genotype 3 and decompensated cirrhosis...
January 2018: Recenti Progressi in Medicina
Darius Babusis, Michael P Curry, Brian Kirby, Yeojin Park, Eisuke Murakami, Ting Wang, Anita Mathias, Nezam Afdhal, John G McHutchison, Adrian S Ray
Sofosbuvir and ribavirin exert their anti-hepatitis C virus (HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplant to prevent HCV reoccurrence provided a unique opportunity to quantify nucleotide concentrations in human liver...
February 12, 2018: Antimicrobial Agents and Chemotherapy
Vinicius Lins Ferreira, Letícia Paula Leonart, Fernanda Stumpf Tonin, Helena Hiemisch Lobo Borba, Roberto Pontarolo
BACKGROUND AND OBJECTIVES: Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained virological response (SVR) presented by clinical trials for these treatments, high rates of effectiveness are also expected in real-world clinical practice. Hence, this study aimed to conduct a systematic review and meta-analysis of observational cohort studies to evaluate the clinical effectiveness and safety of IFN-free therapies for hepatitis C...
February 12, 2018: Clinical Drug Investigation
Yumiko Nagao, Kazunori Nakasone, Tatsuji Maeshiro, Nao Nishida, Kanae Kimura, Yuji Kawahigashi, Yasuhito Tanaka, Michio Sata
Hepatitis C virus (HCV) infection is frequently associated with various extrahepatic manifestations, such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one such extrahepatic manifestation of HCV infection. Recently, direct-acting antivirals (DAA) have proved to be highly effective and safe for the eradication of HCV. Herein, we report a case of OLP accompanied by HCV-related hepatocellular carcinoma (HCC) that disappeared after liver transplantation and achievement of sustained virological response following interferon (IFN)-free treatment with ledipasvir (LDV) and sofosbuvir (SOF)...
September 2017: Case Reports in Gastroenterology
Rania Naiem Sherif, Hussein Abdellatif, Noha Hazem, Neven A Ebrahim, Dalia Saleh, Gamal Shiha, Huda Eltahry, Kamal G Botros, Omar M Gabr
BACKGROUND AND AIM OF THE WORK: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Chronic liver injuries as chronic hepatitis C and hepatitis B viruses, aflatoxins consumption and nonalcoholic fatty liver disease are well-established causes of HCC. HCC is associated with a series of molecular changes, as alternation in glypican-3, P53 expression and Wnt/β-catenin pathway. Hepatic cancer progenitor cells could contribute to HCC development. This research aimed to study the effectiveness of human CD34+ hematopoietic stem cell on Wnt4 and P53 genes expression, histopathological grading and hepatic progenitor cells percentage in HCC rat model...
February 2018: Tissue & Cell
Mitchell L Shiffman
The epidemic of hepatitis C virus (HCV) began in the 1960s when transmission was primarily the result of blood transfusions. By 1990, when HCV was identified and a serologic test for screening donated blood was implemented, 123 million persons had already become infected worldwide and HCV was the most common cause of cirrhosis, hepatocellular carcinoma and the most common indication for liver transplantation. Approximately 75% of persons with HCV are "baby boomers" born between the years 1945 and 1965...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Bruno Roche, Audrey Coilly, Jean Charles Duclos-Vallee, Didier Samuel
Hepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver-related and overall mortality...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Maria J Peláez-Jaramillo, Allison A Cárdenas-Mojica, Paula V Gaete, Carlos O Mendivil
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM...
February 6, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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