Reclassifying Hepatic Cell Death during Liver Damage:Ferroptosis-A Novel Form of Non-Apoptotic Cell Death?

Ferroptosis has emerged as a new type of cell death in different pathological conditions, including neurological and kidney diseases and, especially, in different types of cancer. The hallmark of this regulated cell death is the presence of iron-driven lipid peroxidation; the activation of key genes related to this process such as glutathione peroxidase-4 (gpx4), acyl-CoA synthetase long-chain family member-4 (acsl4), carbonyl reductase [NADPH] 3 (cbr3), and prostaglandin peroxidase synthase-2 (ptgs2); and morphological changes including shrunken and electron-dense mitochondria. Iron overload in the liver has long been recognized as both a major trigger of liver damage in different diseases, and it is also associated with liver fibrosis. New evidence suggests that ferroptosis might be a novel type of non-apoptotic cell death in several liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hemochromatosis. The interaction between iron-related lipid peroxidation, cellular stress signals, and antioxidant systems plays a pivotal role in the development of this novel type of cell death. In addition, integrated responses from lipidic mediators together with free iron from iron-containing enzymes are essential to understanding this process. The presence of ferroptosis and the exact mechanisms leading to this non-apoptotic type of cell death in the liver remain scarcely elucidated. Recognizing ferroptosis as a novel type of cell death in the liver could lead to the understanding of the complex interaction between different types of cell death, their role in progression of liver fibrosis, the development of new biomarkers, as well as the use of modulators of ferroptosis, allowing improved theranostic approaches in the clinic

Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain

The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients

Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

Journal Article;AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the long-term follow-up of cirrhotic patients. METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. Mann-Whitney's U and χ(2) tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy. RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy (18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. Kaplan-Meier curves showed a higher proportion of HE in the group with low phase angle (39%) compared to the normal phase angle group (13%) (P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80 (1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.Ye