Lay Summaries - Volume 3 Issue 4

Lay Summary:  Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, and new evidence suggests that obesity is associated with a disturbed gut bacterial composition, which may influence the development of NAFLD. We examined the composition of bacterial DNA in liver biopsies from healthy lean and obese individuals and found a different composition of bacterial DNA in liver biopsies from the obese group. We propose that the increased bacterial DNA load in the livers of obese individuals could constitute an early risk factor for the progression of NAFLD.
Lay Summary:  The fat content in skeletal muscles (or myosteatosis) is strongly associated with liver stiffness in obese patients with MAFLD. After a dietary intervention, patients in which the degree of myosteatosis decreased also reduced their liver stiffness. The potential contribution of myosteatosis to liver disease progression should be investigated.
Lay Summary:  Protein disulfide isomerase (PDI) family members, and particularly PDIA4, are upregulated and involved in alpha 1-antitrypsin deficiency (AATD)-mediated liver disease in adults. PDI inhibition upon cysteamine treatment leads to improvements in features of AATD and hence represents a therapeutic approach for treatment of AATD-mediated liver disease.
Lay Summary:  People with type 2 diabetes are at increased risk of developing non-alcoholic fatty liver disease and developing more significant complications. This study looks at introducing screening for advanced liver disease into the annual diabetes reviews performed routinely in primary care; we found that significantly more people were identified as having significant liver disease through this pathway than with current standard care.
Lay Summary:  Chronic HBV infection is a leading cause of liver cancer. T cell receptor (TCR)-engineered T cells are patients’ immune cells that have been modified to recognise virus-infected and/or cancer cells. Herein, we evaluated whether mucosal-associated invariant T cells, a large population of unconventional T cells in the liver, could recognise and kill HBV infected hepatocytes when engineered with an HBV-specific TCR. We show that their effector functions may exceed those of conventional T cells currently used in the clinic, including antimicrobial properties and chemokine receptor profiles better suited for targeting liver tumours.
Lay Summary:  HBV infection is an incurable, chronic disease with few available treatments. Addressing this unmet medical need has been hampered by a lack of suitable cell culture models to study the entire viral life cycle in a single experimental setup. We developed an image-based approach suitable to screen large numbers of drugs, using a cell line that can be infected by HBV and produces large amounts of virus particles. By transferring viral supernatants from these infected cells to uninfected target cells, we could monitor the entire viral life cycle. We used this system to screen drug libraries and identified novel anti-HBV inhibitors that potently inhibit HBV in various phases of its life cycle. This assay will be an important new tool to study the HBV life cycle and accelerate the development of novel therapeutic strategies.
Lay Summary:  Resolution of CHB requires the induction of strong cellular immune responses. We used the yellow fever vaccine as a vector for HBV antigens and show that it is capable of inducing high levels of HBV-specific T cells that produce multiple cytokines simultaneously and are cytotoxic in vivo.
Lay Summary:  Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.
Lay Summary:  The prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival.
Lay Summary:  Lineage tracing revealed that zone 3 hepatocytes residing in the pericentral niche have high neoplastic potential. Under chronic liver injury, hepatocytes receiving Wnt/β-catenin signalling broadly exist across all hepatic zones and significantly contribute to liver tumorigenesis as well as liver regeneration. Wnt/β-catenin signalling is a potential drug target for the prevention of hepatocellular carcinoma.
Lay Summary:  Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually responds to immunosuppressive therapy. Serum transaminases and IgG levels within the normal ranges define complete biochemical remission and are considered as surrogate markers for histological disease activity. Here, we show that those biochemical markers are not sufficient to indicate low disease activity in patients with AIH and already established cirrhosis. Consequently, until better biomarkers for disease activity are found, only liver biopsy can reliably indicate disease activity in the presence of cirrhosis. Additional investigations, such as measurements of liver stiffness, should be undertaken to monitor non-invasively for disease progression in patients with AIH and established cirrhosis.
Lay Summary:  Patients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.
Lay Summary:  We showed that PRO-C3 levels were stable under conditions conforming with hospital sample-handling requirements. We determined a healthy reference range and showed that PRO-C3 levels were not associated with sex, age, BMI, or ethnicity. Finally, we provide further evidence of an association of PRO-C3 with increasing liver fibrosis.
Lay Summary:  Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis.