Liver Meeting Draws 11,000 to Vienna

An estimated 11,000 attendees from 105 countries are converging in Vienna, Austria for the 50^th International Liver Congress, hosted by the European Association for the Study of the Liver (ILC/EASL) . Some 200 journalists -- including a team from MD Magazine -- are on hand to report the news.

Eagerly awaited trials include those of two drugs that show promise for treating a common liver disease associated with obesity, known medically as non-alcoholic steatohepatitis (NASH) and its precursor non-alcoholic fatty liver disease (NAFLD).

Those results are due to be presented April 23 after an address by Markus Peck, the EASL secretary general opens the meeting.

Liver disease is a huge and growing burden, particularly in nations where people are growing more obese, and the pharmaceutical industry is also well represented at the meeting, many with news of promising new treatments.

NAFLD affects up to 25% of the U.S. population, a rate that could climb to 50% by 2030. Early-stage NAFLD is marked by increased fat in the liver stored as triacylglycerol (TAG), which is often caused by obesity and/or insulin resistance.

William Wilkison, PhD, chief operating officer of Islet Sciences in Raleigh, NC, will be presenting the results of a trial of remogliflozin etabonate (Islet Sciences). The drug has been shown to reduce glucose levels and increase insulin sensitivity in diabetic patients. In June 2014, in a poster session at the International Society of Endocrinology and the Endocrine Society (ENDO) meeting in Chicago, IL, reported that the drug also appears effective in treating NASH and NAFLD.

According to the research presented at ENDO, obese mice treated orally with remogliflozin etabonate for 4 weeks displayed reduced liver transaminases (AST and ALT; 35% and 80%, respectively)--biomarkers for NAFLD/NASH, compared to controls.

The drug is a selective sodium glucose transporter 2 (SGLT2) inhibitor as well as an anti-oxidant. Islet also observed a reduction in liver transaminases in its 12-week Phase 2b study of remogliflozin etabonate in diabetic patients.

Treatment of diet-induced fat mice with remogliflozin etabonate also resulted in significantly reduced liver weight (50%) as well as total liver TAG content (40%), compared to controls. In another study performed with genetically obese mice, an approximately 50% decrease in liver triglycerides was observed after 8 weeks of oral remogliflozin etabonate treatment. Remogliflozin etabonate also demonstrated robust in vivo anti-oxidant activity, reducing the level of oxidative stress markers, both in plasma and in the liver (30%), compared to controls.

The company said the finding appears to be due to a unique property of active remogliflozin, which also demonstrated greater than ten times the antioxidant activity of canagliflozin and dapagliflozin when measured by oxygen radical antioxidant capacity in vitro.

NAFLD affects up to 25% of the U.S. population, and may reach as high as 50% by 2030. Early stage NAFLD is marked by increased fat in the liver stored as triacylglycerol (TAG), which is often caused by obesity and/or insulin resistance. Researchers theorize that fatty liver (hepatic steatosis), combined with changes in lipid metabolism, create a highly lipotoxic environment characterized by an increase in oxidative cellular stress and resultant decrease in liver function.

If not treated, NAFLD can progress to more severe NASH, which can cause significant scarring of the liver and development of cirrhosis and other serious complications. There are no therapies approved specifically for treating NAFLD/NASH, although anti-diabetic medications and anti-oxidants are being examined based on these important hallmarks of the disease.

EASL attendees will also learn more about another liraglutide (Saxenda/ NovoNordisk) another NASH drug showing promise.

Matthew Armstrong, MD a research fellow in hepatology at the School of Immunity and Infection at the Centre for Liver Research at the University of Birmingham, UK,

and Philip Newsome, the university's head of cell therapy and a professor of experimental hepatologyare due to present the latest research on the pharmaceutical.

An article in The Lancet last year, Anderson reported on a phase 2 study of liraglutide, a glucagon-like peptide-1 analog. In that article he said liraglutide “significantly improves glycemic control, weight and hepatic steatosis.”

In his study, a substudy of the LEAN trial, 14 patients with NASH got daily injections of the drug for 12 weeks.

“Liraglutide significantly decreased weight, waist circumference, HbA1c, fasting glucose, LDL, and liver enzymes compared with placebo,” Anderson wrote, “Liraglutide significantly increased the suppression of hepatic glucose production with low-dose insulin [and] decreased circulating non-esterified fatty acid (NEFA) in the fasting, low-dose, and high-dose insulin states.” Further, he wrote “Liraglutide significantly reduced the insulin concentration required to half-maximally suppress circulating NEFA and significantly decreased adipose tissue lipolysis, as shown by a reduction in interstitial fluid glycerol concentrations.” The serum markers of adipose inflammation—leptin, adiponectin, and hemokine ligand 2—were also reduced.

He concluded “Liraglutide significantly reduces metabolic dysfunction, hepatic lipogenesis, hepatic and adipose insulin resistance, and adipose inflammation in patients with NASH,” and that GLP-1 analogue therapy might be a novel treatment for patients with this condition.

Thursday’s presentations will also include a report on exome sequencing of liver tumors and the research’s implications for new drug targets and new findings on the use of ledipasvir/sofosbuvir with ribarin for liver transplant patients with HCV infection, preliminary results of a trial called SOLAR2.