Lay Summaries - Volume 73 Issue 1

    NAFLD and Alcohol-Related Liver Diseases
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    Javier Ampuero, Rocío Aller, Rocío Gallego-Durán, Javier Crespo, José Luis Calleja, Carmelo García-Monzón, Judith Gómez-Camarero, Joan Caballería, Oreste Lo Iacono, Luis Ibañez, Javier García-Samaniego, Agustín Albillos, Rubén Francés, Conrado Fernández-Rodríguez, Moisés Diago, Germán Soriano, Raúl J. Andrade, Raquel Latorre, Francisco Jorquera, Rosa María Morillas, Desamparados Escudero, Pamela Estévez, Manuel Hernández Guerra, Salvador Augustín, Jesús M. Banales, Patricia Aspichueta, Salvador Benlloch, José Miguel Rosales, Javier Salmerón, Juan Turnes, Manuel Romero Gómez on behalf of the HEPAmet Registry
    Journal of Hepatology, Vol. 73, Issue 1, p17–25
Lay Summary:  Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
Lay Summary:  Patients with non-alcoholic steatohepatitis (NASH) can develop scarring of the liver (fibrosis), including cirrhosis, which increases the risks of liver failure and liver cancer. We tested whether 48 weeks of treatment with selonsertib reduced fibrosis in patients with NASH and advanced liver scarring. We did not find that selonsertib reduced fibrosis in these patients.
Lay Summary:  Especially under infection conditions, it has been difficult to study the different hepatitis B virus transcripts in depth. This study introduces a new method that can be used in any standard lab to discriminate all hepatitis B viral transcripts in cell culture and in the serum of patients.
Lay Summary:  In recent years, studies examining the role of B cells during chronic hepatitis B virus infection have regained interest. We show that circulating B cells more often target the hepatitis B core antigen than the hepatitis surface antigen. Moreover, these hepatitis B core-specific B cells associate with the natural history of chronic HBV, and their responses decline during effective antiviral treatment.
Lay Summary:  We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.
Lay Summary:  Although direct-acting antivirals (DAAs) are successfully used for the treatment of chronic hepatitis C virus (HCV) infection, a prophylactic HCV vaccine needs to be developed, especially for patients who achieve a sustained virologic response. In the current study, we show that a DNA vaccine (GLS-6150) was safe and increased HCV-specific T cell responses. A clinical trial is underway to test this vaccine in patients with a sustained virologic response following DAA therapy.
Lay Summary:  This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.
Lay Summary:  Primary sclerosing cholangitis (PSC) is a long-term disease that damages the bile ducts in the liver over time. In the AESOP clinical study in patients with PSC, obeticholic acid reduced serum alkaline phosphatase (a potential marker of disease severity) during an initial 24-week treatment period. The result was sustained during the 2-year, long-term extension of the study. The most common side effect of obeticholic acid in the study was itchy skin, which is consistent with earlier clinical studies.
Lay Summary:  Toll-like receptor 4 (or TLR4) mediates endotoxin-induced tissue injury in liver failure and cirrhosis. This receptor sensitizes cells to endotoxins, which are produced by gram-negative bacteria. Thus, inhibiting TLR4 signaling with an inhibitor (TAK-242) ameliorates organ injury and systemic inflammation in rodent models of acute and acute-on-chronic liver failure.
Lay Summary:  People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.
Lay Summary:  It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.
    Liver Transplantation
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    Laurent Savale, Manuel Guimas, Nathan Ebstein, Marie Fertin, Mitja Jevnikar, Sébastien Renard, Delphine Horeau-Langlard, Cécile Tromeur, Céline Chabanne, Grégoire Prevot, Ari Chaouat, Pamela Moceri, Élise Artaud-Macari, Bruno Degano, Romain Tresorier, Clément Boissin, Hélène Bouvaist, Anne-Claire Simon, Marianne Riou, Nicolas Favrolt, Sylvain Palat, Delphine Bourlier, Pascal Magro, Vincent Cottin, Emmanuel Bergot, Nicolas Lamblin, Xavier Jaïs, Audrey Coilly, François Durand, Claire Francoz, Filomena Conti, Philippe Hervé, Gérald Simonneau, David Montani, Jean-Charles Duclos-Vallée, Didier Samuel, Marc Humbert, Pascal De Groote, Olivier Sitbon
    Journal of Hepatology, Vol. 73, Issue 1
Lay Summary:  Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
Lay Summary:  Fatty liver disease commonly occurs alongside obesity and diabetes, contributing to rapidly increasing rates of liver cancer throughout the world. Herein, we show that exercise reduces the incidence and progression of hepatocellular carcinoma in mouse models. The effect of exercise on cancer risk was shown to be independent of changes in weight. Exercise could be a protective mechanism against liver cancer in at-risk individuals.
Lay Summary:  Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
Lay Summary:  Integrin αvβ3 expression on activated hepatic stellate cells (aHSCs) is associated with HSC proliferation during hepatic fibrogenesis. Herein, we show that a radioactive tracer, [18F]-Alfatide, binds to integrin αvβ3 with high affinity and specificity. [18F]-Alfatide could thus be used as a non-invasive imaging biomarker to track hepatic fibrosis progression.