Once-daily treatment with glecaprevir-pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157 .).

Leptin signaling is involved in T-cell polarization and is required for profibrotic function of hepatic stellate cells (HSCs). Leptin-deficient ob/ob mice do not develop liver fibrosis despite the presence of severe long-standing steatohepatitis. Here, we blocked leptin signaling with our recently generated mouse leptin antagonist (MLA), and examined the effects on chronic liver fibrosis in vivo using the chronic thioacetamide (TAA) fibrosis model, and in vitro using freshly-isolated primary HSCs. In the chronic TAA fibrosis model, leptin administration was associated with significantly enhanced liver disease and a 100% 5-week to 8-week mortality rate, while administration or coadministration of MLA markedly improved survival, attenuated liver fibrosis, and reduced interferon ␥ (IFN-␥)

Vanadium is a nutritional element present in mammalian tissues. Low quantities of dietary vanadium may be required for normal metabolism in higher animals. Vanadium exhibits a complex chemistry, fluctuating between several different oxidation states and hydrolytic forms, depending on the prevailing conditions. Intracellular forms of vanadium fluctuate between the anionic vanadate (vanadium(+5); H 2 VO 4 -) and the cationic vanadyl (vanadium(+4); hydrated VO 2+ ). Although much research has been performed on vanadium compounds during the last two decades, its physiological function is still obscured (1, 2). A remarkable finding was the induction of normoglycemia in diabetic rodents following oral vanadium therapy (4-7). In vitro studies revealed that vanadium salts virtually mimic most of the effects of insulin (8-10). A number of reviews have been recently published on the potential usage of vanadium as a therapeutic antidiabetic agent (11-14). This review focuses on the mechanisms by which vanadate facilitates its insulin-like effects at the molecular level. Insulin-like effects of vanadateA major role of insulin in mammals is the regulation of glucose homeostasis by modulating glucose production in the liver and glucose utilization in muscle and fat. Reduced potency of insulin to arrest hepatic glucose output or to enhance glucose utilization in peripheral tissues leads to insulin resistance. This phenomenon is accompanied with a compensatory over-secretion of insulin by the pancreas (hyperinsulinemia). A failure of the pancreas to secrete insulin in sufficient quantities leads to hyperglycemia (3).The insulin-like effects of vanadium were originally found in intact cells. Subsequently, vanadium was administrated orally to diabetic animals. In vanadatetreated STZ-rats, hyperglycemia was reduced to normal glucose levels within 2-5 days. Sodium metavanadate in drinking water was found to be optimal at a concentration of 0.2 mg/ml, and in some instances normoglycemia persisted after termination of vanadium therapy (4-6). The effect of vanadate was also determined 308