Lay Summaries - Volume 75 Issue 1

Lay Summary:  Activation of the farnesoid X receptor (FXR) is a clinically validated approach for treating non-alcoholic steatohepatitis (NASH), although side effects such as itching or increases in low-density lipoprotein cholesterol are frequently dose-limiting. MET409, an FXR agonist with a unique chemical structure, led to significant liver fat reduction and delivered a favorable side effect profile after 12 weeks of treatment in patients with NASH. These results provide the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced.
Lay Summary:  Cyclin M4 (CNNM4) is overexpressed in non-alcoholic steatohepatitis (NASH) and promotes the export of magnesium from the liver. The liver-specific silencing of Cnnm4 ameliorates NASH by reducing endoplasmic reticulum stress and promoting the activity of microsomal triglyceride transfer protein.
Lay Summary:  This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health.
    Viral Hepatitis
  • Abstract Image
    Thomas Horvatits, Jan-Erik Wißmann, Reimar Johne, Martin H. Groschup, Ashish K. Gadicherla, Julian Schulze zur Wiesch, Martin Eiden, Daniel Todt, Rudolph Reimer, Lisa Dähnert, Anja Schöbel, Karoline Horvatits, Rabea Lübke, Christine Wolschke, Francis Ayuk, Meike Rybczynski, Ansgar W. Lohse, Marylyn M. Addo, Eva Herker, Marc Lütgehetmann, Eike Steinmann, Sven Pischke
    Journal of Hepatology, Vol. 75, Issue 1, p55–63
    Open Access
Lay Summary:  Enveloped hepatitis E virus particles could be identified by PCR and electron microscopy in the ejaculate of immunosuppressed chronically infected patients, but not in immunocompetent experimentally infected pigs or in patients with acute self-limiting hepatitis E.
Lay Summary:  Viral replication in host cells is defined by the cellular microenvironment and one key factor is local oxygen tension. Hepatitis B virus (HBV) replicates in the liver, a naturally hypoxic organ. Hypoxia inducible factors (HIFs) are the major sensors of low oxygen; herein, we identify a new role for these factors in regulating HBV replication, revealing new therapeutic targets.
Lay Summary:  There remain many unknowns about the natural history of HBV infection in adults. Herein, we identified new HBV-host mechanisms which could be responsible for self-restricting infections. Targeting these mechanisms could be a promising strategy for the treatment of HBV infections.
    DILI, Autoimmune, Cholestatic and Genetic Diseases
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    Camilla Stephens, Mercedes Robles-Diaz, Inmaculada Medina-Caliz, Miren Garcia-Cortes, Aida Ortega-Alonso, Judith Sanabria-Cabrera, Andres Gonzalez-Jimenez, Ismael Alvarez-Alvarez, Mahmoud Slim, Miguel Jimenez-Perez, Rocio Gonzalez-Grande, M. Carmen Fernández, Marta Casado, German Soriano, Eva Román, Hacibe Hallal, Manuel Romero-Gomez, Agustin Castiella, Isabel Conde, Martin Prieto, Jose Maria Moreno-Planas, Alvaro Giraldez, J. Miguel Moreno-Sanfiel, Neil Kaplowitz, M. Isabel Lucena, Raúl J. Andrade, Participating clinical centres
    Journal of Hepatology, Vol. 75, Issue 1, p86–97
    Open Access
Lay Summary:  Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.
Lay Summary:  Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.
Lay Summary:  Abbreviated MRI (AMRI) has been suggested as an alternative to ultrasound and complete MRI for hepatocellular carcinoma (HCC) screening. Our study results showed that AMRI has a high per-patient and per-lesion sensitivity for HCC. Although the sensitivity of AMRI for detection of HCC <2 cm is considerably lower than for HCC ≥2 cm, it is substantially higher than ultrasound, making it a potential alternative for HCC screening in high-risk populations.
Lay Summary:  TBX3 is a liver-specific target of the Wnt/β-catenin pathway and thought to be an oncogene in promoting liver cancer development. Herein, we demonstrate that TBX3 is in fact a tumor suppressor gene that restricts liver tumor growth. Strategies which increase TBX3 expression and/or activities may be effective for HCC treatment.
Lay Summary:  Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.
Lay Summary:  The coronary artery disease in liver transplantation (CAD-LT) score and algorithm effectively stratify patients based on their risk of significant coronary artery disease. The CAD-LT algorithm can be used to guide a more targeted cardiac evaluation prior to liver transplantation.
Lay Summary:  The molecular mechanisms linking endoplasmic reticulum stress to non-alcoholic fatty liver disease (NAFLD) progression remain undefined. Herein, via in vitro and in vivo analysis, we identified Forkhead box A3 (FOXA3) as a key bridging molecule. Of pathophysiological significance, FOXA3 protein levels were increased in livers of obese mice and patients with NAFLD, indicating that FOXA3 could be a potential therapeutic target in fatty liver disease.
Lay Summary:  Several interleukin (IL)-20 family cytokines have been shown to play important roles in controllimg inflammatory responses, infection and tissue damage, but the role of IL-20 remains unclear. Herein, we elucidated the role of IL-20 in liver disease and bacterial infection. We show that IL-20 can aggravate hepatitis and bacterial infection; thus, targeting IL-20 holds promise for the treatment of patients with liver disease.
Lay Summary:  Some patients who receive immunotherapy for cancer develop liver inflammation, which requires cessation of cancer treatment. Herein, we describe ways in which the white blood cells of patients who develop liver inflammation differ from those of patients who receive the same immunotherapy but do not experience liver-related side effects. Targeting some of the pathways we identify may help to prevent or manage this side effect and facilitate cancer treatment.