Lubiprostone Well-Tolerated in NAFLD Trial

August 21, 2020

No life-threatening adverse events occurred in the 150 patient trial to treat non-alcoholic fatty liver disease.

A new trial testing lubiprostone in patients with non-alcoholic fatty liver disease (NAFLD) has proven safe and effective, warranting more research.

A team, led by Takaomi Kessoku, MD, Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, assessed the efficacy and safety of lubiprostone, a laxative known to improve intestinal permeability in health individuals, for patients with non-alcoholic fatty liver disease with constipation through attenuation of intestinal permeability.

In the randomized, double-blind, placebo-controlled, phase 2a study, the investigators examined patients between 20-85 years old with NAFLD and constipation. Each participant had a alanine aminotransferase (ALT) of at least 40 U/L, liver stiffness (≤6.7 kPa), and hepatic fat fraction at least 5.2% when assessed by MRI-proton density fat fraction.

Overall, the team screened 288 patients between March 2017 and April 2018, 150 of which were randomly assigned to treatment.

Each patient was randomly assigned (11:10:9) and stratified by age and sex to receive either 24 μg lubiprostone (n = 55), 12 μg lubiprostone (n = 50), or placebo (n = 45), orally, once per day for 12 weeks.

The investigators sought primary endpoints of the absolute changes in ALT at 12 weeks.

They also conducted efficacy analysis by intention to treat and assessed safety in all treated patients.

The investigators found a greater decrease in the absolute ALT levels from baseline to 12 weeks in the 24 μg lubiprostone group (mean, −13 U/L; SD 19) than in the placebo group (1 U/L; SD, 24; mean difference, −15 U/L; 95% CI, −23 to −6; P = 0.0007) and in the 12 μg lubiprostone group (−12 U/L; SD, 21) than in the placebo group (mean difference, −13 U/L; 95% CI, –22 to −5; P = 0.0023).

A total of 18 (33%) individuals in the 24 μg group had at least one adverse event, while 3 (6%) of patients in the 12 μg group and 3 (7%) individuals in the placebo group experienced at least 1 adverse event.

The most common adverse events found in the study were diarrhea (n = 17; 31%) in the 24 μg group. Diarrhea was also found in the 12 μg group (n = 3; 6%), but did not occur once in the placebo arm of the study.

“Lubiprostone was well tolerated and reduced the levels of liver enzymes in patients with NAFLD and constipation,” the authors wrote. “Further studies are necessary to better define the efficacy and tolerability of lubiprostone in patients with NAFLD without constipation.”

NAFLD is a condition where excess fat is stored in the liver. However, this condition does not usually cause symptoms and is most often found when blood tests indicate elevated liver enzymes.

When the fat builds up, it can cause inflammation and damage, causing non-alcoholic steatohepatitis (NASH), which can lead to scarring of the liver and cirrhosis.

Non-alcoholic fatty liver disease is often linked to obesity, with the prevalence of both diseases becoming increasingly notable. Research indicates that NAFLD is found in 40-80% of individuals who have type 2 diabetes and 30-90% of people who are obese.

However, there is a lack of effective treatments currently available for NAFLD, leading to many researchers taking alternative approaches for new treatments. There are currently no medicines approved by the US Food and Drug Administration (FDA) to treat NAFLD.

The study, “Lubiprostone in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled, phase 2a trial,” was published online in The Lancet Gastroenterology& Hepatology.