Nov 4 2014
A common drug used to clean a person's bowels before a colonoscopy could become the future standard of care for patients with acute hepatic encephalopathy (HE), a mental disorientation problem that affects up to one in two cirrhosis patients. The finding comes from new research, known as the "HELP Clinical Trial," that appeared in JAMA Internal Medicine on Sept. 22.
Led by Robert Rahimi, MD, of the Baylor University Medical Center, the study compared the current HE treatment, lactulose, with polyethylene glycol 3350-electrolyte solution (PEG) otherwise known as GoLYTELY®, an oral medicine used to clean out the intestines before a colonoscopy. The PEG solution has been FDA-approved for intestinal cleansing since 1984, but until now has never been tested for use in acute HE.
"Lactulose has been the standard of care for many years, dating back to the 1960s. However, the efficacy hasn't really been looked at in greater detail, but rather adopted," said Dr. Rahimi, a transplant hepatologist who focuses his research on HE. "But if you look at the high-quality studies from a Cochrane meta-analysis, lactulose is actually no better than placebo. So we hypothesized that by purging the gastrointestinal tract with PEG, we could potentially improve outcomes in patients hospitalized for acute HE."
Faster, Improved Outcomes
In the small-scale trial, a total of 50 HE-afflicted participants were divided into two groups of 25, with one group receiving lactulose (standard therapy) and the other group receiving the PEG solution (new therapy). About 91 percent of the PEG patients rapidly improved compared with 52 percent of the lactulose patients. No adverse side effects were reported.
Additionally, patients who received the PEG solution had a shorter hospital stay than the lactulose participants.
"On average, [the hospital stay for acute HE] can be about five days overall, depending on the underlying precipitant," Dr. Rahimi said. "In patients who took the PEG solution, HE resolved one day quicker. So there's an overall potential for decreased length of stay, which could result in cost savings."
The Ammonia/Ammonium Conundrum
As a severe complication linked with cirrhosis, HE takes place when ammonia builds up in a patient's blood. When someone eats protein, their body produces the ammonia, a toxic byproduct that's typically removed by a healthy liver. But in patients whose livers can't function properly because of cirrhosis, the ammonia remains in the body.
When that happens, the patient may experience a range of mental symptoms - from trouble sleeping to forgetfulness, poor concentration and confusion. At the surface, HE patients may appear drunk, but the issue is significantly more serious than intoxication and can cause coma or death. HE occurs in up to 45 percent of cirrhosis patients and often requires hospitalization.
"Hepatic encephalopathy is a common and terrible problem for many patients with cirrhosis," said Don Rockey, MD, a gastroenterologist at the Medical University of South Carolina, who also took part in the research. "It is also extremely disruptive for families and is difficult to treat with current medicines when it becomes severe enough to require hospitalization."
The current treatment, lactulose, is a special kind of laxative that has been used to treat HE for half a century. For years, hepatologists have suspected that it works by converting ammonia into ammonium, which prevents the ammonia from dissolving into the patient's blood. But lately, consensus on that point is hard to come by.
"There have been a number of studies that have looked at it a different way, so the jury's not out on that," Dr. Rahimi said. "We do understand that the ammonia is the main pathophysiological aspect of hepatic encephalopathy, but there are many other underlying causes that we don't quite understand. So maybe it's not all ammonia, and there is something else going on."
Those mixed sentiments have led to new hypotheses about what actually treats a person's HE symptoms. The new evidence suggests that instead of the ammonia-ammonium conversion, a powerful intestinal flush - like the kind used for colonoscopies - may be the best way to address acute HE.
Hope for a New Standard of Care
While it is possible that the PEG solution could become standardized for acute HE in the next few years, Dr. Rahimi said, there is a need for more research beyond this pilot trial. With continuing studies, he said, investigators may better understand what actually triggers and treats HE in cirrhosis patients.
His team plans to launch future research on the topic that would involve several facilities across the country, Baylor included. As those clinical trials take place, investigators could learn new insights to not only treat acute HE, but in some cases prevent it.
"Because lactulose is the standard of care for outpatients as well, this new research might lead to different medicines that can be used from an outpatient standpoint, which could help prevent patients from even getting hospitalized in the first place," he said. "That's the hope."
SOURCE HealthTexas Provider Network