Lay Summaries - Volume 74 Issue 6

Lay Summary:  Alcohol use treatments, including physician counseling and medication-assisted therapies (MATs), improve the outcomes of patients with compensated alcohol-related cirrhosis, though use and access have remained suboptimal. In this study, we found that counseling and MATs are extremely cost-effective, and in some cases cost-saving, interventions to help patients with alcohol-related cirrhosis abstain from alcohol and improve their health. Wider use of these interventions should be encouraged.
Lay Summary:  Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.
Lay Summary:  Occult hepatitis B virus infections (OBIs) have been found to be associated with amino acid mutations in the S region of the HBV, but the role of mutations in the core protein (Cp) remains unclear. In this study, an OBI strain (SZA) carrying 9 amino acid substitutions in Cp has been examined comprehensively in vitro and in vivo. The W62R mutation in Cp majorly reduces HBcAg and HBeAg production during HBV replication, potentially contributing to the occurrence of OBI.
Lay Summary:  Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.
    DILI, Autoimmune, Cholestatic and Genetic Diseases
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    Eleonora De Martin, Audrey Coilly, Olivier Chazouillères, Olivier Roux, Jean-Marie Peron, Pauline Houssel-Debry, Florent Artru, Christine Silvain, Isabelle Ollivier-Hourmand, Christophe Duvoux, Alexandra Heurgue, Sandrine Barge, Nathalie Ganne-Carrié, Georges-Philippe Pageaux, Camille Besch, Marc Bourlière, Hélène Fontaine, Victor de Ledinghen, Jérôme Dumortier, Filomena Conti, Sylvie Radenne, Marilyne Debette-Gratien, Odile Goria, François Durand, Pascal Potier, Vincent Di Martino, Noemi Reboux, Philippe Ichai, Mylène Sebagh, Philippe Mathurin, Hélène Agostini, Didier Samuel, Jean-Charles Duclos-Vallée, the FILFOIE consortium – France
    Journal of Hepatology, Vol. 74, Issue 6, p1325–1334
Lay Summary:  The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
    DILI, Autoimmune, Cholestatic and Genetic Diseases
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    Thomas Marjot, Gustav Buescher, Marcial Sebode, Eleanor Barnes, A. Sidney Barritt IV, Matthew J. Armstrong, Luke Baldelli, James Kennedy, Carolyn Mercer, Ann-Kathrin Ozga, Christian Casar, Christoph Schramm, contributing Members and Collaborators of ERN RARE-LIVER/COVID-Hep/SECURE-Cirrhosis, Andrew M. Moon, Gwilym J. Webb, Ansgar W. Lohse
    Journal of Hepatology, Vol. 74, Issue 6, p1335–1343
    Open Access
Lay Summary:  Little is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from 3 large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system.
Lay Summary:  Patients with primary biliary cholangitis (a rare chronic liver disease) that do not respond to standard therapy remain at risk of disease progression toward cirrhosis and impaired quality of life. Elafibranor is a nuclear receptor agonist that we tested in a randomized clinical trial over 12 weeks. It successfully decreased levels of disease activity markers, including alkaline phosphatase. Thus, this study is the foundation for a larger prospective study that will determine the efficacy and safety of this drug as a second-line therapy.
Lay Summary:  In patients with cirrhosis listed for liver transplantation, the presence of multiorgan failure, a condition referred to as acute-on-chronic liver failure, is associated with high waiting list mortality rates. Current organ allocation policy disadvantages patients with this condition. This study describes and validates a new scoring method that performs better than the currently available scoring systems. Further validation of this approach may reduce the deaths of patients with cirrhosis and acute-on-chronic liver failure on the transplant waiting list.
    Cirrhosis and Liver Failure
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    Dominik Bettinger, Lukas Sturm, Lena Pfaff, Felix Hahn, Roman Kloeckner, Lara Volkwein, Michael Praktiknjo, Yong Lv, Guohong Han, Jan Patrick Huber, Tobias Boettler, Marlene Reincke, Christoph Klinger, Karel Caca, Hauke Heinzow, Leon Louis Seifert, Karl Heinz Weiss, Christian Rupp, Felix Piecha, Johannes Kluwe, Alexander Zipprich, Hendrik Luxenburger, Christoph Neumann-Haefelin, Arthur Schmidt, Christian Jansen, Carsten Meyer, Frank E. Uschner, Maximilian J. Brol, Jonel Trebicka, Martin Rössle, Robert Thimme, Michael Schultheiss
    Journal of Hepatology, Vol. 74, Issue 6, p1362–1372
Lay Summary:  Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.
Lay Summary:  The growth of many cancers is sustained by a specific type of cells with more embryonic characteristics, termed ‘cancer stem cells’. These cells have been described in cholangiocarcinoma, a type of liver cancer with poor prognosis and limited therapeutic approaches. We demonstrate that cancer stem cells in cholangiocarcinoma have different metabolic features, and use mitochondria, an organelle located within the cells, as the major source of energy. We also identify PGC-1α, a molecule which regulates the biology of mitochondria, as a possible new target to be explored for developing new treatments for cholangiocarcinoma.
Lay Summary:  The NKG2D system is a potent immunosurveillance mechanism in cancer. However, its role in hepatocellular carcinoma development has not been widely investigated. Herein, we should that the expression of NKG2D ligands by tumour cells is associated with a more aggressive tumour subtype.
Lay Summary:  We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.
Lay Summary:  Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.
Lay Summary:  This report describes the development of an innovative mRNA therapy as a potential treatment for PFIC3, a devastating rare paediatric liver disease with no treatment options except liver transplantation. We show that administration of our mRNA construct completely rescues severe liver disease in a genetic model of PFIC3 in mice.
Lay Summary:  Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.