Lay Summaries - Volume 73 Issue 2

Lay Summary:  A medicine called volixibat has previously been shown to reduce cholesterol levels in the blood. This study investigated whether volixibat could reduce the amount of fat in the liver and reduce liver injury in adults with an advanced form of non-alcoholic fatty liver disease. Volixibat did not reduce the amount of fat in the liver, nor did it have any other beneficial effect on liver injury. Participants in the study generally tolerated the side effects of volixibat and, as in previous studies, the main side effect was diarrhoea. These results show that volixibat is not an effective treatment for people with fatty liver disease.
Lay Summary:  We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.
Lay Summary:  The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
Lay Summary:  Non-alcoholic fatty liver disease, type 2 diabetes and obesity are epidemiologically correlated with each other, but their causal relationships were incompletely understood. Herein, we identified causal relationships between these conditions, which suggest that each of these closely related diseases should be further stratified into subtypes. This is important for accurate diagnosis, prevention and treatment of these diseases.
Lay Summary:  Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.
Lay Summary:  Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.
Lay Summary:  Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint.
Lay Summary:  Patients with severe alcoholic hepatitis are at increased risk of infections, which contribute to the poor prognosis associated with the disease. Herein, we show that epigenetic determinants underly the immune cell dysfunction and inappropriate responses to pathogens that are associated with severe alcoholic hepatitis.
    Hepatic and Biliary Cancer
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    Robert Montal, Daniela Sia, Carla Montironi, Wei Q. Leow, Roger Esteban-Fabró, Roser Pinyol, Miguel Torres-Martin, Laia Bassaganyas, Agrin Moeini, Judit Peix, Laia Cabellos, Miho Maeda, Carlos Villacorta-Martin, Parissa Tabrizian, Leonardo Rodriguez-Carunchio, Giancarlo Castellano, Christine Sempoux, Beatriz Minguez, Timothy M. Pawlik, Ismail Labgaa, Lewis R. Roberts, Manel Sole, Maria I. Fiel, Swan Thung, Josep Fuster, Sasan Roayaie, Augusto Villanueva, Myron Schwartz, Josep M. Llovet
    Journal of Hepatology, Vol. 73, Issue 2, p315–327
Lay Summary:  Targeted therapies have not been approved for the treatment of extrahepatic cholangiocarcinoma. We performed a multi-platform molecular characterization of this tumor in a cohort of 189 patients. These analyses revealed 4 novel transcriptome-based molecular classes of extrahepatic cholangiocarcinoma and identified ∼25% of tumors with actionable genomic alterations, which has potential prognostic and therapeutic implications.
    Hepatic and Biliary Cancer
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    Juan Carrillo-Reixach, Laura Torrens, Marina Simon-Coma, Laura Royo, Montserrat Domingo-Sàbat, Jordi Abril-Fornaguera, Nicholas Akers, Margarita Sala, Sonia Ragull, Magdalena Arnal, Núria Villalmanzo, Stefano Cairo, Alberto Villanueva, Roland Kappler, Marta Garrido, Laura Guerra, Constantino Sábado, Gabriela Guillén, Mar Mallo, David Piñeyro, María Vázquez-Vitali, Olga Kuchuk, María Elena Mateos, Gema Ramírez, Manuel López Santamaría, Yasmina Mozo, Aroa Soriano, Michael Grotzer, Sophie Branchereau, Nagore García de Andoin, Blanca López-Ibor, Ricardo López-Almaraz, José Antonio Salinas, Bárbara Torres, Francisco Hernández, José Javier Uriz, Monique Fabre, Julià Blanco, Claudia Paris, Viera Bajčiová, Geneviève Laureys, Helena Masnou, Ariadna Clos, Cristina Belendez, Catherine Guettier, Lauro Sumoy, Ramón Planas, Mireia Jordà, Lara Nonell, Piotr Czauderna, Bruce Morland, Daniela Sia, Bojan Losic, Marie Annick Buendia, Maria Rosa Sarrias, Josep M. Llovet, Carolina Armengol
    Journal of Hepatology, Vol. 73, Issue 2, p328–341
    Open Access
Lay Summary:  Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.
Lay Summary:  In the context of liver transplantation for patients with hepatocellular carcinoma, prediction models are used to ensure that the risk of recurrence after transplantation is acceptably low. The Metroticket 2.0 model has been proposed as an accurate predictor of “tumour-related death” after liver transplantation. In the present study, we show that its accuracy can be improved by incorporating information relating to the radiological responses of patients to neoadjuvant therapies.
Lay Summary:  After an overdose of acetaminophen (paracetamol), some patients present to hospital too late for the current antidote (N-acetylcysteine) to be effective. We tested whether macrophages, an injury-responsive leukocyte that can scavenge dead/dying cells, could serve as a cell-based therapy in an experimental model of acetaminophen overdose. Injection of alternatively activated macrophages rapidly reduced liver injury and reduced several mediators of inflammation. Macrophages show promise to serve as a potential cell-based therapy for acute liver injury.
Lay Summary:  Expression of the immune regulator PU.1 is increased in livers of obese mice and people. Blocking PU.1 improved glucose homeostasis, and reduced liver steatosis, inflammation and fibrosis in mouse models of non-alcoholic steatohepatitis. Inhibition of PU.1 is thus a potential therapeutic strategy for treating obesity-associated liver dysfunction and metabolic diseases.
Lay Summary:  Specific RNA sequences called G-quadruplexes (or RG4) appear to be important in post-transcriptional gene regulation. Obesity leads to the formation of these RG4 structures in pre-miR-26a-1 molecules, impairing the maturation and function of miR-26a, which has emerged as a therapeutic target in several diseases. This contributes to hepatic insulin resistance and the dysregulation of liver metabolism.
Lay Summary:  A novel murine peptide hormone, herein named ‘metabolitin’, inhibits fatty acid absorption and improves systemic insulin resistance in a murine model of obesity and non-alcoholic fatty liver disease. Thus, metabolitin has therapeutic potential for the treatment of patients with non-alcoholic fatty liver disease.