Lay Summaries - Volume 68 Issue 1

Lay Summary: Serum HBV-RNA levels are indicative of the intrahepatic transcriptional activity of covalently closed circular DNA and are associated with liver histological changes in patients with chronic B hepatitis who are receiving nucleos(t)ide analogue therapy.
Lay Summary: It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.
    Viral Hepatitis
  • Abstract Image
    Aimilia Karampatou, Xue Han, Loreta A. Kondili, Gloria Taliani, Alessia Ciancio, Filomena Morisco, Rosina Maria Critelli, Enrica Baraldi, Veronica Bernabucci, Giulia Troshina, Maria Guarino, Simonetta Tagliavini, Federica D'Ambrosio, Laura Bristot, Laura Turco, Stefano Rosato, Stefano Vella, Tommaso Trenti, Isabella Neri, Antonio La Marca, Shivaji Manthena, Andrea S. Goldstein, Savino Bruno, Yanjun Bao, Yuri Sanchez Gonzalez, Erica Villa, PITER framework investigators, PITER Investigators
    Journal of Hepatology, Vol. 68, Issue 1, p33–41
    Open Access
Lay Summary: Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.
Lay Summary: Hepatitis B virus (HBV) replication occurs efficiently in human liver because of the specificity of viral uptake receptors and presence of numerous liver-enriched transcription activators. Herein, we show that the specific lack of transcriptional inhibitory mechanisms in liver cells also contribute to effective HBV production. HBV replication is kept low in non-liver cells as transcriptional repressors Slug and SRY-related HMG box 7 (SOX7) actively bind to the transcriptional initiator and displace transcription activators, respectively, within the HBV core promoter.
Lay Summary: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.
Lay Summary: We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance.
Lay Summary: Bleeding from oesophageal or gastric varices is a severe complication of cirrhosis, related to an increased pressure in the portal vein perfusing the liver. Some patients are described as “severe”, either because their liver disease is already severe, or because the bleeding is very important. Those patients could benefit from a prothesis, placed inside the liver by an interventional radiologist, aiming to decrease the pressure in the portal vein, just after the control of bleeding by medications and endoscopic treatment. New studies are warranted to demonstrate a real beneficial effect of this therapeutic attitude, which is not adopted in real-life practice, as shown by this national French audit of practice.
Lay Summary: An increasing number of donor livers contain fat. It is important to harness marginal livers, which may contain fat, as the stock of donor livers is limited. Hypothermic oxygenated perfusion (HOPE) prevents reperfusion injury and improves liver graft function. HOPE offers a simple and low-cost option for treating liver grafts in transplant centers, even after cold storage, instead of transporting machines to the place of procurement. HOPE could be used globally to expand the donor pool.
Lay Summary: HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.
Lay Summary: A delay of ≥3 months in time to resection after diagnosis in HCC patients meeting the European Association for the Study of Liver Disease/American Association for the Study of Liver Disease criteria for resection does not affect oncological and long-term outcomes compared to those with a delay to surgery of <3¯months.
Lay Summary: In mild ALD, ST2 negatively regulates the inflammatory activation of hepatic macrophages, thereby protecting against alcohol-induced liver damage, whereas in the case of severe liver injury, the release of extracellular IL-33 may exacerbate tissue inflammation by triggering the canonical IL-33/ST2L signaling in hepatic macrophages.
Lay Summary: Reductions in the level of the protein Dusp14 are closely associated with liver damage caused by inadequate blood supply followed by restoration of blood flow to the liver. Dusp14 protects against liver damage by suppressing the activity of Tak1. Targeting Dusp14 could be a strategy for prevention and treatment of this disease.
Lay Summary: Liver ischemia and reperfusion injury results in the formation of neutrophil extracellular traps, which contribute to organ damage in liver surgeries. Herein, we show that IL-33 is released from liver sinusoidal endothelial cells to promote NET formation during liver I/R, which exacerbates inflammatory cascades and sterile inflammation.
Lay Summary: Non-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular carcinoma (HCC). There have been limited data on the association between NAFLD and extrahepatic cancers. This study demonstrated that patients with NAFLD showed a higher association with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NAFLD fibrosis score and a high fibrosis-4 score showed a strong association with the development of all cancers and HCC.
Lay Summary: In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.
Lay Summary: Drug development in hepatocellular carcinoma (HCC) has been characterised by many failures in the past. Despite good rationales and promising phase II data, many phase III trials failed. Immunotherapy represents an alternative treatment approach that has been successful in many different cancer types. As an inflammation induced cancer, HCC represents a very interesting target for immune based approaches. Indeed, early results from clinical trials testing immune checkpoint inhibitors are not only promising, but have already led to evaluation in a phase III setting. Herein, we summarise our current knowledge on the rationale, mechanism of action and clinical data for immune checkpoint blockade in HCC. In addition, we provide an overview of other novel immune based approaches currently under development for the treatment of HCC, such as adoptive cell based and antibody-based approaches.