New Insights Into Constipation, NAFLD Prevention, and IBS Treatment

Researchers reported on factors that can prevent nonalcoholic fatty liver disease (NAFLD) and reduce symptoms of chronic constipation or diarrhea-predominant irritable bowel syndrome (IBS-D) at the American College of Gastroenterology’s annual meeting last week in Philadelphia.

Philadelphia

Philadelphia

In an oral presentation, Huafen Shen (Nassau University Medical Center) described the association between aspirin use and the prevalence of NAFLD in a general US population, based on a cross-sectional analysis of data from the 3rd National Health and Nutrition Examination Survey. Aspirin has been previously shown to inhibit multiple pathways involved in development of NAFLD.

Shen’s group analyzed data from 11,416 adults who underwent ultrasonography (2889 with NAFLD and 8527 controls). Data were then collected on whether subjects had never used (0 times), occasionally used (1±14 times), or regularly used (≥15 times) aspirin in the month before they were interviewed.

After controlling age, sex, ethnicity, socioeconomic status, body mass index, physical activity, smoking status, insulin resistance, blood pressure, and lipid levels, Shen and colleagues associated regular aspirin use with low prevalence of NAFLD (odds ratio, 0.62).

The prevalence of NAFLD was lower among occasional and regular aspirin users who were male (odds ratios of 0.58 and 0.32, respectively) or older than 60 years (OR 0.74 and 0.21, respectively), compared with those that did not use aspirin. The prevalence of NAFLD was not reduced among women or younger subjects who took aspirin.

Shen proposed that aspirin might reduce the risk for NAFLD via its anti-oxidant activities. He said that women have greater urinary exclusion of aspirin and its metabolites, which could reduce aspirin’s effects.

In another oral presentation, Andres Acosta (Mayo Clinic) reported findings from a phase 2 trial showing that a peptide agonist of the ghrelin receptor (Relamorelinaccelerated upper and lower GI transit and improved symptoms of bowel function in patients with chronic constipation.

Receptors for ghrelin are located in the colon, and although relamorelin has been shown to accelerate gastric emptying shortly after administration, little was known about its effects on colonic motility and constipation in humans.

Acosta’s group gave 48 patients daily subcutaneous injections of placebo for 2 weeks, and then the ghrelin agonist (100 ug) or placebo for 2 weeks. Based reports from subjects’ daily bowel diaries, patients in the ghrelin agonist group had 5.34 spontaneous bowel movements/week, compared with 3.67/week in the placebo group. The ghrelin agonist group had 3.38 complete bowel movements per week, compared with 2.46 per week in the placebo group.

“A total of 60% had their first bowel movement within 10 hours after the first dose,” Acosta said.

According to MedPage Today, the ghrelin agonist also increased small bowel transit time and colonic filling at 6 hours (61.5 vs 42.9), and colon transit at 32 hours (2.96 vs 2.29) and 48 hours (3.32 vs 2.70).

In the following oral presentation, Anthony Lembo (Harvard Medical School and Beth Israel Deaconess Medical Center) reported that administration of rifaximin to patients with IBS-D significantly reduced symptoms, and that treatment can be repeated successfully in patients who relapse.

Lembo showed that in an open-label study of 2579 patients, 42% responded to 2 weeks of treatment, based on the FDA criteria of at least a 30% reduction in pain and a ≥50% decrease in the number of days with scores or 6 (loose) or 7 (watery) on the Bristol Stool Scale.

Among the initial responders, 36% never relapsed during 18 to 22 weeks of follow up.

When the 64% who did relapse were evaluated in a second, blinded study, a 2-week course of rifaximin induced a response in 33%, compared with 25% in those receiving placebo. The finding is important because these were more refractory patients, the study’s co-author Mark Pimentel told MedPage Today.

After the second treatment course, those who again relapsed were given a 3rd course of rifaximin or placebo; 37% of the rifaximin group responded compared with 29% of the placebo group.

“The main message of the study is that if you are retreated, you continue to have benefit for IBS, and there have been no new safety concerns,” Lembo told MedPage Today.

Rifaximin is currently approved for hepatic encephalopathy and travelers’ diarrhea; an FDA ruling on approval for IBS is expected in February 2015.

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