Lay Summaries - Volume 77 Issue 1

    NAFLD and Alcohol-Related Liver Diseases
  • Abstract Image
    Marcos F. Fondevila, Uxia Fernandez, Violeta Heras, Tamara Parracho, Maria J. Gonzalez-Rellan, Eva Novoa, Begoña Porteiro, Cristina Alonso, Rebeca Mayo, Natalia da Silva Lima, Cristina Iglesias, Aveline A. Filliol, Ana Senra, Teresa C. Delgado, Ashwin Woodhoo, Laura Herrero, Dolors Serra, Vincent Prevot, Markus Schwaninger, Miguel López, Carlos Dieguez, Oscar Millet, Jose M. Mato, Francisco J. Cubero, Marta Varela-Rey, Paula Iruzubieta, Javier Crespo, Maria L. Martinez-Chantar, Robert F. Schwabe, Ruben Nogueiras
    Journal of Hepatology, Vol. 77, Issue 1, p15–28
    Open Access
Lay Summary:  We show that the enzyme carnitine palmitoyltransferase 1A (CPT1A) is elevated in hepatic stellate cells (HSCs) in patients with fibrosis and mouse models of fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs.
Lay Summary:  Chronic hepatitis C virus (HCV) infection can lead to hepatocellular carcinoma development in a process that involves derangement of the extracellular matrix (ECM). Herein, we show that heparanase-1, a protein involved in ECM degradation and remodeling, favors HCV infection and is upregulated by HCV infection; this upregulation may result in pathogenic alterations of the ECM.
Lay Summary:  Functional cure can be sustained in a proportion of patients with chronic hepatitis B after pegylated interferon alpha-based treatment. However, predicting who will achieve durable functional cure remains challenging. Herein, we show that low levels of hepatitis B core-related antigen and higher levels of hepatitis B surface antibodies at the end of treatment are linked to immunological responses and are associated with durable functional cure.
Lay Summary:  Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.
Lay Summary:  Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.
    DILI, Autoimmune, Cholestatic and Genetic Diseases
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    Ahmed Ghallab, Reham Hassan, Ute Hofmann, Adrian Friebel, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe, Maiju Myllys, Joerg Reinders, Nina Overbeck, Selahaddin Sezgin, Sebastian Zühlke, Abdel-latif Seddek, Walaa Murad, Tim Brecklinghaus, Franziska Kappenberg, Jörg Rahnenführer, Daniela González, Christopher Goldring, Ian M. Copple, Rosemarie Marchan, Thomas Longerich, Mihael Vucur, Tom Luedde, Stephan Urban, Ali Canbay, Thomas Schreiter, Michael Trauner, Jephte Y. Akakpo, Mojtaba Olyaee, Steven C. Curry, Jan-Peter Sowa, Hartmut Jaeschke, Stefan Hoehme, Jan G. Hengstler
    Journal of Hepatology, Vol. 77, Issue 1, p71–83
    Open Access
Lay Summary:  Only one drug, N-acetylcysteine, is approved for the treatment of acetaminophen overdose and it is only effective when given within ∼8 hours after ingestion. We identified a mechanism by which acetaminophen overdose causes an increase in bile acid concentrations (to above toxic thresholds) in hepatocytes. Blocking this mechanism prevented acetaminophen-induced hepatotoxicity in mice and evidence from patients suggests that this therapy may be effective for longer periods after ingestion compared to N-acetylcysteine.
Lay Summary:  Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.
Lay Summary:  People with cirrhosis are often malnourished and this has a detrimental effect on outcome. Provision of an adequate diet is very important and is best achieved by measuring daily energy requirements and adjusting dietary intake accordingly. Prediction equations, which use information on age, sex, weight, and height can be used to estimate energy requirements; however, the results they provide are not accurate enough for clinical use, particularly as they vary according to sex and ethnicity.
Lay Summary:  In a nationwide US cohort of hospitalized patients with cirrhosis and acute kidney injury, acute kidney disease developed in 1 in 3 patients and was associated with worse survival and chronic kidney disease. Interventions that target acute kidney disease may improve outcomes of patients with cirrhosis and acute kidney injury.
Lay Summary:  Immune and inflammatory gene signatures may be associated with increased sensitivity to immunotherapy in patients with advanced hepatocellular carcinoma. In the present study, the use of artificial intelligence-based pathology enabled us to predict the activation of these signatures directly from histology.
Lay Summary:  There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed.
Lay Summary:  The increase in deaths due to hepatocellular carcinoma (HCC) is a growing concern, with the mechanisms responsible for HCC development still incompletely understood. Herein, we identify a novel mechanism by which the protein PARG contributes to HCC development. Inhibition of PARG increased the efficacy of anti-PD-1 therapy (a type of immunotherapy) in HCC. These findings support the future clinical development of PARG inhibitors, potentially in combination with anti-PD-1 inhibitors.
Lay Summary:  The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.
Lay Summary:  Despite remarkable treatment progress, most patients with hepatocellular carcinoma respond poorly to anti-PD1 therapy (a type of immunotherapy). A deeper insight into the tolerance mechanisms to this therapy is urgently needed. Herein, we unravel a previously unexplored mechanism linking tumor progression, macrophage polarization, and anti-PD1 resistance, and offer an attractive novel target for anti-PD1 combination therapy, which may benefit patients with hepatocellular carcinoma.
Lay Summary:  Little is known about the role of post-translational modifications of proteins in cholangiocarcinoma development and progression. Herein, we show that protein NEDDylation is upregulated and hyperactivated in cholangiocarcinoma, promoting tumor growth. Pharmacological inhibition of NEDDylation halts cholangiocarcinogenesis and could be an effective therapeutic strategy to tackle these tumors.