Lay Summaries - Volume 5 Issue 1

Lay Summary:  Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.
Lay Summary:  This study has shown that people who regularly perform greater amounts of physical activity have a reduced level of inflammation and fibrosis in their liver. This beneficial relationship is particularly strong when more intense physical activity is undertaken (i.e., vigorous-intensity), and is most visible in individuals with higher levels of liver fat and body fat.
Lay Summary:  SCYL3 was first reported to be a binding partner of a metastasis-related gene, ezrin. To date, the clinical relevance and functional role of SCYL3 in cancer remain uncharacterized. Herein, we uncover its crucial role in liver cancer progression. We show that it physically binds and regulates the stability and transactivating activity of ROCK2 leading to HCC tumor progression. Our data provide mechanistic insight that SCYL3-mediated ROCK2 protein stability plays a pivotal role in growth and metastasis of HCC cells. Targeting SCYL3/ROCK2 signaling cascade may be a novel therapeutic strategy for treatment of HCC patients.
Lay Summary:  Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.
Lay Summary:  Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).
Lay Summary:  Visceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of “good” HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.
    Research Articles
  • Abstract Image
    Bernhard Scheiner, Daniel Roessler, Samuel Phen, Mir Lim, Katharina Pomej, Tiziana Pressiani, Antonella Cammarota, Thorben W. Fründt, Johann von Felden, Kornelius Schulze, Vera Himmelsbach, Fabian Finkelmeier, Ansgar Deibel, Alexander R. Siebenhüner, Kateryna Shmanko, Pompilia Radu, Birgit Schwacha-Eipper, Matthias P. Ebert, Andreas Teufel, Angela Djanani, Florian Hucke, Lorenz Balcar, Alexander B. Philipp, David Hsiehchen, Marino Venerito, Friedrich Sinner, Michael Trauner, Antonio D'Alessio, Claudia A.M. Fulgenzi, David J. Pinato, Markus Peck-Radosavljevic, Jean-François Dufour, Arndt Weinmann, Andreas E. Kremer, Amit G. Singal, Enrico N. De Toni, Lorenza Rimassa, Matthias Pinter
    JHEP Reports, Vol. 5, Issue 1
Lay Summary:  Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy.
Lay Summary:  This study investigated the prevalence of weak social relationships in individuals with cirrhosis and their influence on health-related quality of life and risk of mortality. Individuals with cirrhosis were nearly twice as likely to report low social support, loneliness, and to live alone than a matched comparison cohort. Low social support and loneliness (functional measures of social relationships) were associated with lower mental health-related quality of life and increased risk of mortality risk in cirrhosis, when adjusting for known confounders. We hope that these results will make healthcare providers aware of the functional aspects of the social relationships of individuals with cirrhosis, in addition to the traditional clinical management, and motivate further research of interventions to strengthen the social support of individuals with cirrhosis.
Lay Summary:  Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH.
Lay Summary:  The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.
Lay Summary:  Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.
Lay Summary:  Despite potential improvements in mental health after successful treatment with direct-acting antivirals, many people living with HIV (PLWH) and hepatitis C virus (HCV) - even in older age classes - still face depressive symptoms after HCV cure. In this population, women and people reporting unhealthy alcohol use, sedentary lifestyle, or unhealthy eating behaviors are more prone to report depressive symptoms after HCV cure. Mental health and lifestyle-related issues should be integrated in a global care model for PLWH living with or having a history of hepatitis C.