Lay Summaries - Volume 76 Issue 3

Lay Summary:  Non-alcoholic fatty liver disease is a chronic hepatic disease that can progress to non-alcoholic steatohepatitis (NASH), which is associated with an increased risk of cirrhosis and liver cancer. Results from this phase II study support continued development of EDP-305, an oral farnesoid X receptor agonist, for the treatment of patients with NASH.
Lay Summary:  We conducted an epidemiological study on the potential effect of ambient air pollution on the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in approximately 90 thousand adults in China. We found that long-term exposure to ambient air pollution may increase the odds of MAFLD, especially in individuals who are male, smokers, and alcohol drinkers, those who consume a high-fat diet, and those with central obesity.
Lay Summary:  The pathogenesis of non-alcoholic fatty liver disease can be explained in part by a metabolic component, including obesity, and in part by a genetic component. Herein, we demonstrate that the mechanisms underlying these components are fundamentally different: the metabolic component is characterized by hepatic oversupply of substrates, such as sugars, lipids and amino acids. In contrast, the genetic component is characterized by impaired hepatic mitochondrial function, making the liver less able to metabolize these substrates.
Lay Summary:  Non-alcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, non-invasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study, which is evaluating the effects of obeticholic acid vs. placebo in patients with NASH, various NITs were also evaluated. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients’ response to therapy.
Lay Summary:  Increased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.
Lay Summary:  Interventions to treat drug-induced liver injury and halt its progression into liver failure are of great value to society. The present study reveals that muscle-liver cross talk, with MG53 as a messenger, serves an important role in liver cell protection. Thus, MG53 is a potential treatment option for patients with drug-induced liver injury.
    DILI, Autoimmune, Cholestatic and Genetic Diseases
  • Abstract Image
    Amandine Landemaine, Houda Hamdi-Roze, Séverine Cunat, Véronique Loustaud-Ratti, Xavier Causse, Si Nafa Si Ahmed, Bernard Drénou, Christophe Bureau, Gilles Pelletier, Caroline De Kerguenec, Nathalie Ganne-Carrie, Stéphane Durupt, Fabrice Laine, Olivier Loréal, Martine Ropert, Lenaick Detivaud, Jeff Morcet, Patricia Aguilar-Martinez, Yves M. Deugnier, Edouard Bardou-Jacquet
    Journal of Hepatology, Vol. 76, Issue 3, p568–576
Lay Summary:  Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.
Lay Summary:  Sebelipase alfa is used to treat lysosomal acid lipase deficiency (LAL-D), a rare, inherited disease of lipid metabolism. We report the final results of the phase III ARISE clinical study, which show that replacement of the defective LAL enzyme with sebelipase alfa for up to 5 years allows adults and children 4 years of age and older to maintain their initial improvements in liver and cholesterol parameters over the long term, without worsening of liver disease.
    Cirrhosis and Liver Failure
  • Abstract Image
    Xinxing Tantai, Yi Liu, Yee Hui Yeo, Michael Praktiknjo, Ezequiel Mauro, Yuhei Hamaguchi, Cornelius Engelmann, Peng Zhang, Jae Yoon Jeong, Jeroen Laurens Ad van Vugt, Huijuan Xiao, Huan Deng, Xu Gao, Qing Ye, Jiayuan Zhang, Longbao Yang, Yaqin Cai, Yixin Liu, Na Liu, Zongfang Li, Tao Han, Toshimi Kaido, Joo Hyun Sohn, Christian Strassburg, Thomas Berg, Jonel Trebicka, Yao-Chun Hsu, Jan Nicolaas Maria IJzermans, Jinhai Wang, Grace L. Su, Fanpu Ji, Mindie H. Nguyen
    Journal of Hepatology, Vol. 76, Issue 3, p588–599
    Open Access
Lay Summary:  The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.
Lay Summary:  Since it is harder to collect stool than saliva, we wanted to test whether microbes from saliva were better than stool in differentiating between healthy people and those with cirrhosis and, among those with cirrhosis, those with more severe disease. Using machine learning, we found that microbes in stool were more accurate than saliva alone or in combination, therefore, stool should be preferred for analysis and collection wherever possible.
Lay Summary:  Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses.
Lay Summary:  Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.
Lay Summary:  The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation.
Lay Summary:  Metabolic liver disease and viral hepatitis are common chronic liver diseases and risk factors of hepatocellular carcinoma, which are often associated with impaired hepatic autophagy and increased mTOR activation. Using multiple genetically engineered mouse models of defective hepatic autophagy and persistent mTOR activation, we dissected the complex mechanisms behind this observation. Our results uncovered an unexpected novel tumor suppressor function of p62/Sqstm1, which regulated liver cell repopulation, ductular reaction and metabolic reprogramming in liver tumorigenesis.
Lay Summary:  Sox9, a marker of liver progenitor cells and bile duct lining cells, is a downstream target of YAP protein activation. Herein, we found that YAP activation in hepatocytes leads to a transition from mature hepatocytes to liver progenitor cells and then to bile duct lining cells. Sox9 is required in the second step during mouse hepatocarcinogenesis. We also found that human YAP and SOX9 may play similar roles in liver cancers.