A Multi-Intervention Campaign Lowers Pediatric and Young Adult Diabetic Ketoacidosis Hospitalizations in a Canadian Province.

Objectives: The Newfoundland and Labrador diabetic ketoacidosis Project (NLdkaP) is a multi-intervention, province-wide project aimed at lowering rates of diabetic ketoacidosis (DKA) within the pediatric and young adult populations.

Methods: The NLdkaP interventions were first selected, developed and implemented. We then conducted a retrospective study of hospitalization data over three 2-year periods: pre-, during and post-NLdkaP.

Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis.

Background & Aims: Non-alcoholic steatohepatitis is a leading cause of end-stage liver disease. Hepatic steatosis and lipotoxicity cause chronic necroinflammation and direct hepatocellular injury resulting in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Emricasan is a pan-caspase inhibitor that inhibits excessive apoptosis and inflammation; it has also been shown to decrease portal pressure and improve synthetic function in mice with carbon tetrachloride-induced cirrhosis.

A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, and lobular inflammation which may lead to fibrosis. Lipotoxicity activates caspases, which cause apoptosis and inflammatory cytokine (IL-1β and IL-18) production. Emricasan is a pan-caspase inhibitor that decreases serum aminotransferases and caspase activation in patients with NASH.

Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension.

Background & Aims: Emricasan, an oral pan-caspase inhibitor, decreased portal pressure in experimental cirrhosis and in an open-label study in patients with cirrhosis and severe portal hypertension, defined as a hepatic venous pressure gradient (HVPG) ≥12 mmHg. We aimed to confirm these results in a placebo-controlled study in patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis.

Methods: We performed a multicenter double-blinded study, randomizing 263 patients with NASH-related cirrhosis and baseline HVPG ≥12 mmHg to twice daily oral emricasan 5 mg, 25 mg, 50 mg or placebo in a 1:1:1:1 ratio for up to 48 weeks.