Lay Summaries - Volume 69 Issue 1

Lay Summary: The efficacy of the new direct-acting antivirals is associated with a significant improvement in survival of patients undergoing liver transplantation because of hepatitis C virus-related liver disease. In addition, it has decreased the number of patients with hepatitis C that need a liver transplant.
Lay Summary: Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.
Lay Summary: In contrast to hepatitis B virus, infection with hepatitis D virus induces a strong IFN-ß/? response in innate immune competent cell lines. MDA5 is the key sensor for the recognition of hepatitis D virus replicative intermediates. An IFN-activated state did not prevent hepatitis D virus replication in vitro, indicating that hepatitis D virus is resistant to self-induced innate immune responses and therapeutic IFN treatment.
Lay Summary: The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.
Lay Summary: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60?years, ventilator status, diabetes, hemodialysis and creatinine >1.5?mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival.
Lay Summary: Acetaminophen (APAP) induced acute liver failure because of over dose is a leading public health problem. APAP-induced liver injury exhibits diurnal variation, specifically APAP causes more severe liver damage when taken at night compared with in the morning. Herein, we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione is involved in the rhythmic hepatotoxicity induced by APAP, by depleting hepatic glutathione (an important antioxidant) levels. Our data suggest gut microbiota may be a potential target for reducing APAP-induced acute liver injury.
Lay Summary: We compared the hepatic arterial infusion of FOLFOX (a combination chemotherapy) with sorafenib (a tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma, retrospectively. It was found that hepatic arterial infusion of FOLFOX therapy may improve both progression free and overall survival in patients with advanced hepatocellular carcinoma
Lay Summary: Surgical resection and radiofrequency ablation are both treatment options for perivascular hepatocellular carcinoma. We compared outcomes in patients treated with either method. Surgical resection provided better long-term tumor control and overall survival than radiofrequency ablation for patients with a small perivascular hepatocellular carcinoma (=3?cm) as a first-line treatment, particularly for periportal tumors. The location of the tumor and the type of peritumoral hepatic vessels need to be considered when choosing between surgical resection and radiofrequency ablation for small HCCs
Lay Summary: Primary liver cancer is a malignant disease with poor prognosis, largely because there are limited systemic therapies available. We show here that a cytoplasmic tyrosine phosphatase Shp2 is required for liver tumorigenesis. This tumorigenesis is driven by two oncoproteins that are implicated in human liver cancer. This, together with our previous studies, uncovers the complexity of liver tumorigenesis, by elucidating the pro- and anti-tumor effects of Shp2 in mouse models. This data can be used to guide new therapies.
Lay Summary: We applied multiregional whole-exome sequencing to investigate the evolution of intrahepatic cholangiocarcinoma (ICC). The results revealed that many factors, such as parallel evolution and chromosome instability, may participate and promote the branch diversity of ICC. Interestingly, in one patient with primary and recurrent metastatic tumors, we found evidence of polyclonal metastatic seeding, indicating that symbiotic communities of multiple clones existed and were maintained during metastasis. More realistically, some truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, could be promising treatment targets in patients with ICC.
Lay Summary: Glycogen synthase kinase 3ß promotes macrophage inflammatory activation by inhibiting the immune regulatory signalling of AMP-activated protein kinase and the induction of small heterodimer partner. Therefore, therapeutic targeting of glycogen synthase kinase 3ß enhances innate immune regulation and protects liver from ischaemia and reperfusion injury.
Lay Summary: Hepatic ischemia/reperfusion injury is a serious complication that occurs in liver surgery. Herein, we demonstrated that inducible prostaglandin E2 synthase (mPGES-1), an enzyme involved in synthesizing prostaglandin E2, worsens the injury and delays liver repair through accumulation of proinflammatory macrophages. Inhibition of mPGES-1 offers a potential therapy for both liver protection and repair in hepatic ischemia/reperfusion injury.
Lay Summary: Recreational inhalation of ketamine is currently an important substance abuse issue worldwide, and can result in anomalies of the biliary system as demonstrated by magnetic resonance imaging. Although prolonged exposure may lead to further clinical deterioration, such biliary system anomalies might be reversible after ketamine abstinence.
Lay Summary: Alcoholic liver disease is a major cause of morbidity and mortality worldwide. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Our study reveals that deficiency of sorting nexin (SNX) 10 increases the stability of LAMP-2A by inhibiting cathepsin A maturation, resulting in the increase of CMA activity and, thus, alleviates alcohol-induced liver injury and steatosis.
Lay Summary: Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury. Our results demonstrated for the first time the critical roles of apoptosis of enterocytes and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins in promoting this gut leakiness and endotoxemia. These results provide insight into the molecular mechanisms of alcohol-induced inflammatory liver disease.