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    Original Article Open Access
    PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease
    Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Ou-Yang Huang, Rafael S. Rios, Kenneth I. Zheng, Sui-Dan Chen, Hong-Lei Ma, Giovanni Targher, Christopher D. Byrne, Xiao-Yan Pan, Ming-Hua Zheng
    Journal of Clinical and Translational Hepatology, Published online October 22, 2021. doi:10.14218/JCTH.2021.00286
    Abstract
    Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic [...] Read more.
    Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism. The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest. The distribution of PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02–1.04, p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained significantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95% CI: 1.03–1.08 for the GG group; and adjusted-OR:1.03; 95% CI: 1.01–1.04 for the GC group). There was a significant interaction between VFA and PNPLA3 rs738409 genotype (Pinteraction=0.004). PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF. Full article
    Review Article Open Access
    Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science
    Yasser Fouad, Melissa Palmer, Minjun Chen, Arie Regev, Rajarshi Banerjee, Rob Myers, Robert Riccio, Richard Torstenson, Ramy Younes, Puneet S. Arora, Henrik Landgren, Morten A. Karsdal, Martin Blake, David A. Shapiro, Hans-Juergen Gruss, Muhammad Y. Sheikh, Dina Attia, Steven Bollipo, Alastair D. Smith, Bradley Freilich, Robert G. Gish, Detlef Schuppan
    Journal of Clinical and Translational Hepatology, Published online October 22, 2021. doi:10.14218/JCTH.2021.00408
    Abstract
    Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, [...] Read more.
    Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care―including patients, patients’ advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others―we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science. Full article
    Review Article Open Access
    Targeted Mitochondrial Delivery to Hepatocytes: A Review
    Brent D. Heineman, Xiaocong Liu, George Y. Wu
    Journal of Clinical and Translational Hepatology, Published online October 19, 2021. doi:10.14218/JCTH.2021.00093
    Abstract
    Defects in mitochondria are responsible for various genetic and acquired diseases. Mitochondrial transplantation, a method that involves introduction of healthy donor mitochondria [...] Read more.
    Defects in mitochondria are responsible for various genetic and acquired diseases. Mitochondrial transplantation, a method that involves introduction of healthy donor mitochondria into cells with dysfunctional mitochondria, could offer a novel approach to treat such diseases. Some studies have demonstrated the therapeutic benefit of mitochondrial transplantation and targeted delivery in vivo and in vitro within hepatocytes and the liver. This review discusses the issues regarding isolation and delivery of mitochondria to hepatocytes and the liver, and examines the existing literature in order to elucidate the utility and practicality of mitochondrial transplantation in the treatment of liver disease. Studies reviewed demonstrate that mitochondrial uptake could specifically target hepatocytes, address the challenge of non-specific localization of donor mitochondria, and provide evidence of changes in liver function following injection of mitochondria into mouse and rat disease models. While potential benefits and advantages of mitochondrial transplantation are evident, more research is needed to determine the practicality of mitochondrial transplantation for the treatment of genetic and acquired liver diseases. Full article
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    Review Article Open Access
    Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease
    Cyriac Abby Philips, Philip Augustine, Praveen Kumar Yerol, Ganesh Narayan Ramesh, Rizwan Ahamed, Sasidharan Rajesh, Tom George, Sandeep Kumbar
    Journal of Clinical and Translational Hepatology, Published online December 11, 2019. doi:10.14218/JCTH.2019.00035
    Abstract
    Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, [...] Read more.
    Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis and cirrhosis, severe alcoholic hepatitis, primary sclerosing cholangitis and hepatic encephalopathy, have strong links to dysbiosis – or a pathobiological change in the microbiota. In this review, we provide clear and concise discussions on the human gut microbiota, methods of identifying gut microbiota and its functionality, liver diseases that are affected by the gut microbiota, including novel associations under research, and provide current evidence on the modulation of gut microbiota and its effects on specific liver disease conditions. Full article
    Review Article Open Access
    Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease
    Daud H. Akhtar, Umair Iqbal, Luis Miguel Vazquez-Montesino, Brittany B. Dennis, Aijaz Ahmed
    Journal of Clinical and Translational Hepatology, Published online November 29, 2019. doi:10.14218/JCTH.2019.00028
    Abstract
    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be [...] Read more.
    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD. Full article
    Review Article Open Access
    The Direct Contribution of Astrocytes and Microglia to the Pathogenesis of Hepatic Encephalopathy
    Victoria Jaeger, Sharon DeMorrow, Matthew McMillin
    Journal of Clinical and Translational Hepatology, Published online November 13, 2019. doi:10.14218/JCTH.2019.00025
    Abstract
    Hepatic encephalopathy is a neurological complication resulting from loss of hepatic function and is associated with poor clinical outcomes. During acute liver failure over 20% of [...] Read more.
    Hepatic encephalopathy is a neurological complication resulting from loss of hepatic function and is associated with poor clinical outcomes. During acute liver failure over 20% of mortality can be associated with the development of hepatic encephalopathy. In patients with liver cirrhosis, 1-year survival for those that develop overt hepatic encephalopathy is under 50%. The pathogenesis of hepatic encephalopathy is complicated due to the multiple disruptions in homeostasis that occur following a reduction in liver function. Of these, elevations of ammonia and neuroinflammation have been shown to play a significant contributing role to the development of hepatic encephalopathy. Disruption of the urea cycle following liver dysfunction leads to elevations of circulating ammonia, which enter the brain and disrupt the functioning of astrocytes. This results in dysregulation of metabolic pathways in astrocytes, oxidative stress and cerebral edema. Besides ammonia, circulating chemokines and cytokines are increased following liver injury, leading to activation of microglia and a subsequent neuroinflammatory response. The combination of astrocyte dysfunction and microglia activation are significant contributing factors to the pathogenesis of hepatic encephalopathy. Full article
Special Features

Call for Papers for Special Issue ‘Acute liver failure (ALF)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Acute liver failure (ALF)
Submission deadline: August 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue:Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)
Submission deadline: May 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Coronavirus Disease (COVID-19) and the Liver’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Coronavirus Disease (COVID-19) and the Liver
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Prevention & Control of Coronavirus Disease (COVID-19)

Journal: Exploratory Research and Hypothesis in Medicine
Special Issue: Prevention & Control of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Treatment of Coronavirus Disease (COVID-19)’

Journal: Journal of Exploratory Research in Pharmacology
Special Issue: Treatment of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted